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You are here: Home / Publications / Bibliographies and Resource Guides / Canine Models in Biomedical Research, 1990-2009  / Nervous System  Printer Friendly Page
Canine Models in Biomedical Research,  1990-2009
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Nervous System

Barros, G.A., M.E. Marques, and E.M. Ganem (2007). The effects of intrathecal administration of betamethasone over the dogs' spinal cord and meninges. Acta Cirurgica Brasileira Sociedade Brasileira Para Desenvolvimento Pesquisa Em Cirurgia 22(5): 361-5. ISSN: 0102-8650.
Abstract: PURPOSE: To determinate the potential clinical and histological changes due the injection of betamethasone, when administered into the canine intrathecal space. METHODS: Twenty one animals were included in a random and blind manner in the study. After general anesthesia, intrathecal puncture was performed and 1 ml of the random solution was injected. The G1 dogs received 0.9% saline solution, the G2 dogs received 1.75 mg betamethasone and the G3 dogs received 3.5 mg of betamethasone. The animals were clinically evaluated for 21 days and then sacrificed. The lumbar and sacral portions of the spinal cord were removed for light microscopy histological analyses. RESULTS: No clinical changes were observed in any of the animals included in this study. No histological changes were observed in G1 animals. Inflammatory infiltration was observed in two dogs, one in G2, another in G3. Hemorrhage and necrosis were also seen in the G2 dog which inflammatory infiltration was detected. In other two dogs, one from G2 and another from G3, there was discreet fibrosis and thickness of the arachnoid layer which was focal in one and diffuse in the other. CONCLUSION: Intrathecal administration of betamethasone caused histological changes in the spinal cord and meninges in some of the dogs involved in this study.
Descriptors: anti inflammatory agents adverse effects, betamethasone adverse effects, meninges drug effects, spinal cord drug effects, analysis of variance, anti inflammatory agents administration and dosage, betamethasone administration and dosage, dogs, fibrosis etiology, inflammation chemically induced, inflammation pathology, injections, spinal, meninges pathology, models, animal, necrosis etiology, random allocation, sodium chloride administration and dosage, spinal cord pathology, spinal puncture.

Bashar, A.H., K. Suzuki, T. Kazui, M.Y. Okada, T. Suzuki, N. Washiyama, H. Terada, and K. Yamashita (2008). Changes in cerebrospinal fluid and blood lactate concentrations after stent-graft implantation at critical aortic segment: a preliminary study. Interactive Cardiovascular and Thoracic Surgery 7(2): 262-6.
Abstract: OBJECTIVES: Obstruction of blood flow through the arteria radicularis magna (ARM) has been linked with ischemic spinal cord injury after conventional thoracic aortic repair. Whether or not endoluminal stent-grafts, deliberately positioned against this artery can cause similar damage to the spinal cord has not been comprehensively investigated. The purpose of this study was to assess the blood and cerebrospinal fluid (CSF) concentrations of lactate - a well-known biochemical marker of ischemic neurological injury, before and after stent-graft implantation against the ARM. MATERIALS AND METHODS: Endoluminal stent-grafting was performed in ten mongrel dogs. In five animals (experimental group), stent-grafts covered the fourth and fifth lumbar segmental arteries - which have been described as the canine equivalents to the ARM in humans. In the remaining five animals (control group), devices of similar length were placed in the lower thoracic aorta. CSF was obtained by cisternal puncture technique at the following time points; before stent-grafting, and 15, 30 and 60 min after stent-grafting. Parallel arterial blood samples were also obtained using a heparinized syringe. All samples were centrifuged and the supernatant analysed for lactate. RESULTS: The mean preprocedural lactate concentration in the CSF was 1.7+/-0.3 mmol/l. Mean postprocedural levels in the experimental group at 15, 30 and 60 min were 3.1+/-1.9, 3.9+/-1.1 and 11.9+/-2.5 mmol/l, respectively (control values; 2.1+/-1.9, 2.7+/-1.1 and 1.9+/-1.5 mmol/l, respectively). Mean preprocedural blood lactate level was 1.8+/-0.6 mmol/l, while the mean postprocedural concentrations in the experimental group at 15, 30 and 60 min were 2.9+/-1.2, 3.4+/-1.7 and 3.9+/-2.0 mmol/l, respectively. Two out of the five animals in the experimental group suffered mild to moderate hind limb weakness. CONCLUSION: Selective placement of stent-grafts against the ARM in dogs resulted in a conspicuous increase in CSF and blood lactate concentrations 60 min after the procedure with or without physical signs of neurological deficits. Although the small sample size of this preliminary study does not allow any definitive conclusion, it may be worthwhile to confirm the findings in appropriately controlled larger studies.
Descriptors: blood vessel prosthesis, blood vessel prosthesis implantation adverse effects, lactic acid metabolism, spinal cord ischemia etiology, stents, thoracic arteries surgery, aortography, biological markers metabolism, blood vessel prosthesis implantation instrumentation, dogs, lactic acid blood, lactic acid cerebrospinal fluid, models, animal, motor activity, pilot projects, prosthesis design, spinal cord ischemia metabolism, spinal cord ischemia physiopathology, thoracic arteries radiography, time factors, up regulation.

Bassiouni, H., R. Schulz, H. Dorge, D. Stolke, and G. Heusch (2007). The impact of subarachnoid hemorrhage on regional cerebral blood flow and large-vessel diameter in the canine model of chronic vasospasm. Journal of Stroke and Cerebrovascular Diseases the Official Journal of National Stroke Association 16(2): 45-51.
Abstract: OBJECTIVE: The aim of this study was to correlate changes in regional cerebral blood flow (rCBF) to the degree of cerebral vasospasm in the canine two-hemorrhage model of subarachnoid hemorrhage (SAH). METHODS: SAH was induced in 13 adult beagle dogs using the two-hemorrhage model. Eleven beagle dogs served as controls. Angiography of the basilar artery and measurements of rCBF with colored microspheres were performed on days 1 and 8. Diameter of the basilar artery was calculated at equidistant points from the angiogram. RESULTS: In controls, basilar artery diameter (mm) and rCBF (mL/min/g) were equal on days 1 and 8. In the SAH group, basilar artery diameter decreased significantly (1.27 +/- 0.17 [mean +/- SD]-0.84 +/- 0.15 mm). rCBF decreased significantly (P < .05) in the cerebrum (1.69 +/- 0.54 [mean +/- SD]-1.06 +/- 0.45 mL/min/g), cerebellum (1.18 +/- 0.40-0.80 +/- 0.32 mL/min/g), and brain stem (0.81 +/- 0.33-0.51 +/- 0.21 mL/min/g). However, decrements in CBF were not correlated to the reduction in vessel caliber in the corresponding vascular territory. CONCLUSION: Induced SAH in the canine model produces a significant impairment in rCBF irrespective of the degree of vasospasm of large cerebral vessels. The findings support the presumptive role of the microvasculature in regard to delayed cerebral ischemia after SAH.
Descriptors: cerebrovascular circulation, subarachnoid hemorrhage physiopathology, vasospasm, intracranial physiopathology, basilar artery pathology, blood flow velocity, brain ischemia etiology, brain ischemia pathology, brain ischemia physiopathology, brain stem blood supply, cerebellum blood supply, dogs, microcirculation, microspheres, models, animal, renal circulation, telencephalon blood supply, vasospasm, intracranial complications, vasospasm, intracranial pathology.

Benczik, J., T. Seppala, M. Snellman, H. Joensuu, G.M. Morris, and J.W. Hopewell (2003). Evaluation of the relative biological effectiveness of a clinical epithermal neutron beam using dog brain. Radiation Research 159(2): 199-209. ISSN: 0033-7587.
NAL Call Number: 334.8 R11
Abstract: This investigation was designed to determine the relative biological effectiveness (RBE) of an epithermal neutron beam (FiR 1 beam) using the brains of dogs. The FiR 1 beam was developed for the treatment of patients with glioma using boron neutron capture therapy. Comparisons were made between the effects of whole-brain irradiation with epithermal neutrons and 6 MV photons. For irradiations with epithermal neutrons, three dose groups were used, 9.4+-0.1, 10.2+-0.1 and 11.5+-0.2 Gy. These physical doses were given as a single exposure and are quoted at the 90% isodose. Four groups of five dogs were irradiated with single doses of 10, 12, 14 or 16 Gy of 6 MV photons to the 100% isodose. Different reference isodoses were used to obtain the most comparable dose distribution in the brain for the two different irradiation modalities. Sequential magnetic resonance images (MRI) were taken for 77-115 weeks after irradiation to detect changes in the brain. Dose-effect relationships were established for changes in the brain as detected either by MRI or by subsequent gross morphology and histology. The doses that caused a specified response in 50% of the animals (ED50) were calculated from these dose-effect curves for each end point, and these values were used to calculate the RBE values for the different end points. The RBE values for the FiR 1 beam, based on changes observed on MRI, were in the range 1.2-1.3. For microscopic and gross pathological lesions, the values were in the range 1.2-1.4. The corresponding RBE values for the MRI and pathological end points for the high-LET components (protons from nitrogen capture and recoil protons from fast neutrons) were in the ranges 3.5-4.0 and 3.4-4.4, respectively. This assumed a dose-rate reduction factor of 0.6 for the low-dose-rate gamma-ray component of this beam. Finally, a comparison was made between experimentally derived photon doses, for a specified end point, with calculated photon equivalent doses, which were obtained using the weighting factors for clinical studies on the epithermal neutron beam on the Brookhaven Medical Research Reactor (BNL) in New York. This indicated that the radiation-induced lesions seen in the present study were, on average, detected at a 12% lower photon dose than predicted by the use of the BNL clinical weighting factors. This indicates the need for caution in the extrapolation of results from one reactor-based epithermal neutron beam to another.
Descriptors: methods and techniques, nervous system, neural coordination, radiation biology, magnetic resonance imaging, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, whole brain irradiation, epithermal neutron beam, relative biological effectiveness.

Bodine, R.E., S.E. Dow, G.D. Smith, and M.J. Kallman (2003). A novel conscious dog model for monitoring electroencephalographic activity. FASEB Journal 17(4-5): Abstract No. 153.8. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: nervous system, neural coordination, pharmacology, tremor, electroencephalography, non-invasive technique, monitoring , electroencephalographic activity.

Boehmer, L.N., M.F. Wu, J. John, and J.M. Siegel (2004). Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity. Experimental Neurology 188(2): 292-299. ISSN: 0014-4886.
Descriptors: breeds, Doberman pinschers, Labrador retrievers, behavior, genetics, nervous system, neural coordination, pharmacology, genetic narcolepsy, behavioral and mental disorders, nervous system disease, therapy .

Brandes, I.F., A.G. Stucke, D. Jakovcevic, C. Dean, F.A. Hopp, E.J. Zuperku, and E.A. Stuth (2004). Characteristics of the effects of locally applied serotonin on the discharge patterns of canine hypoglossal motoneurons (hmns) in vivo. FASEB Journal 18(4-5): Abst. 468.8. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Abstract: Serotonin appears to play a key role in controlling the excitability of HMNs, which contributes to the maintenance of upper airway patency that may become compromised by sleep, anesthetics, potent analgesics and sedatives. The <I>in vivo</I> effects of serotonin on HMNs are incompletely understood. The purpose of this study was to characterize canine HMN responses to serotonin. Multibarrel micropipettes were used to simultaneously record unit activity and picoeject serotonin on HMNs in decerebrate, vagotomized, paralyzed, ventilated dogs. Spike-triggered averaging of hypoglossal nerve activity was used to verify that the recorded neuron was a HMN. Serotonin-induced changes in gain and offset of discharge patterns were analyzed. Dose-response effects were studied by progressive step increases in picoejection rate. Most HMNs displayed phasic activity during the inspiratory phase. As the serotonin dose-rate increased, HMN phasic activity markedly increased primarily through changes in gain (2X). At higher dose-rates, activity during the quiescent expiratory phase also increased resulting in a baseline shift. These results suggest that serotonin may act differentially by increasing the excitability of phasic glutamatergic inputs in most HMNs, while in other neurons it results in a tonic depolarization without gain changes or enhances tonic excitatory inputs. A combination of these two effects was also observed.Supported by NIH grant GM59234 and VA Med. Res. Funds.
Descriptors: biochemistry and molecular biophysics, nervous system, neural coordination.

Carlson, G.D., H.S. Oliff, C. Gorden, J. Smith, and P.A. Anderson (2003). Cerebral spinal fluid pressure: effects of body position and lumbar subarachnoid drainage in a canine model. Spine 28(2): 119-122. ISSN: 0362-2436.
Abstract: Study Design. This study used an in vivo model of subarachnoid cerebrospinal fluid pressure measurement. Objectives. To examine the relation between subarachnoid cerebrospinal fluid pressure in the cervical and lumbar spine and varying body positions, and to test the hypothesis that increasing body inclination and lumbar subarachnoid drainage decreases cervical cerebrospinal fluid pressures. Summary of Background Data. Cerebrospinal fluid leaks are a recognized complication of anteriror posterior cervical surgery. Conflicting opinion exists regarding the benefits of postoperative patient positioning and lumbar subarachnoid drainage. Methods. Subarachnoid cerebrospinal fluid pressure of 7 beagles was monitored via two angiocatheters attached to pressure transducers inserted into the subarachnoid space through laminectomies at C3 and L4. Pressure measurements were taken when body position was inclined to 30degree, 60degree, and 90degree. A lumbar durotomy was performed to simulate the effects of lumbar subarachnoid drainage. The body was repositioned to 90degree, and pressure was measured. Results. As inclination increased from 0degree to 90degree, the mean cervical cerebrospinal fluid pressure significantly decreased. The mean lumbar subarachnoid pressure significantly increased, as inclination increased from 0degree to 90degree. Lumbar durotomy plus repositioning to 90degree resulted in a significant reduction in cervical cerebrospinal fluid subarachnoid pressure, with pressure dropping by 46%. Lumbar cerebrospinal fluid subarachnoid pressure dropped to zero after lumbar durotomy plus repositioning to 90degree. Conclusions. Cerebrospinal fluid pressures in the subarachnoid space of both the cervical and lumbar spines are affected by changes in body position. Both patient positioning and lumbar drainage may be important in reducing cervical cerebrospinal fluid pressure, and may reduce the occurrence of cerebrospinal fluid leaks after primary dural repair in the neck.
Descriptors: models and simulations, computational biology, nervous system, neural coordination, skeletal system, movement and support, dural leak, connective tissue disease, injury, dural tear, angiocatheter, laboratory equipment, cervical surgery, clinical techniques, therapeutic and prophylactic techniques, laminectomy, experimental surgical techniques, laboratory techniques, lumbar durotomy, experimental surgical techniques, pressure transducer, laboratory equipment, body position, cerebral spinal fluid pressure, in vivo model, lumbar subarachnoid drainage, postoperative complications, subarachnoid pressure.

Cooper, J.J., C. Ashton, S. Bishop, R. West, D.S. Mills, and R.J. Young (2003). Clever hounds: social cognition in the domestic dog (canis familiaris). Applied Animal Behaviour Science 81(3): 229-244. ISSN: 0168-1591.
NAL Call Number: QL750.A6
Abstract: This paper reviews the reasons why domestic dogs make good models to investigate cognitive processes related to social living and describes experimental approaches that can be adopted to investigate such processes in dogs. Domestic dogs are suitable models for investigating social cognition skills for three broad reasons. First, dogs originated from wolves, social animals that engage in a number of co-operative behaviours, such as hunting and that may have evolved cognitive abilities that help them predict and interpret the actions of other animals. Second, during domestication dogs are likely to have been selected for mental adaptations for their roles in human society such as herding or companionship. Third, domestic dogs live in a human world and "enculturation" may facilitate the development of relevant mental skills in dogs. Studies of social cognition in animals commonly use experimental paradigms originally developed for pre-verbal human infants. Preferential gaze, for example, can be used as a measure of attention or "surprise" in studies using expectancy violation. This approach has been used to demonstrate simple numerical competence in dogs. Dogs also readily use both conspecific and human social signals (e.g. looking or pointing) as information sources to locate hidden rewards such as food or favourite toys. Such abilities make dogs particularly good models for investigating perspective-taking tasks, where animals are required to discriminate between apparently knowledgeable and apparently ignorant informants.
Descriptors: behavior, evolution and adaptation, neural coordination, attention, companionship, counting, domestication, evolution, herding, hunting, mental skills, numerical competence, preferential gaze, reward, social cognition.

Durand, D.M. (2007). Neural engineering--a new discipline for analyzing and interacting with the nervous system. Methods of Information in Medicine 46(2): 142-6. ISSN: 0026-1270.
Abstract: OBJECTIVES: The field of neural engineering focuses on an area of research at the interface between neuroscience and engineering. The area of neural engineering was first associated with the brain machine interface but is much broader and encompasses experimental, computational, and theoretical aspects of neural interfacing, neuroelectronics, neuromechanical systems, neuroinformatics, neuroimaging, neural prostheses, artificial and biological neural circuits, neural control, neural tissue regeneration, neural signal processing, neural modelling and neuro-computation. One of the goals of neural engineering is to develop a selective interface for the peripheral nervous system. METHODS: Nerve cuffs electrodes have been developed to either reshape or maintain the nerve into an elongated shape in order to increase the circumference to cross sectional ratio. It is then possible to place many electrodes around the nerve to achieve selectivity. This new cuff (flat interface nerve electrode: FINE) was applied to the hypoglossal nerve and the sciatic nerve in dogs and cats to estimate the selectivity of the interface. RESULTS: By placing many contacts close to the axons, three different types of selectivity were achieved: 1) The FINE could generate a high degree of stimulation selectivity as estimated by the individual fascicle recording. 2) Similarly, recording selectivity was also demonstrated and blind source algorithms were applied to recover the signals. 3) Finally, by placing arrays of electrodes along the nerve, small fiber diameters could be excited before large fibers thereby reversing the recruitment order. CONCLUSION: Taking advantage of the fact that nerves are not round but oblong or flat allows a novel design for selective nerve interface with the peripheral nervous system. This new design has found applications in many disorders of the nervous system such as bladder incontinence, obstructive sleep apnea and stroke.
Descriptors: central nervous system, electrodes, implanted, nerve tissue physiology, peripheral nerves physiology, prostheses and implants, signal processing, computer assisted, algorithms, dogs, hypoglossal nerve physiology, models, animal, models, biological, sciatic nerve physiology.

Furukawa, N., M. Hatano, and E. Nakamura (2003). Antro-pancreatic reflexes: long- and short-route reflexes in exocrine and endocrine pancreatic secretion in dogs. Autonomic Neuroscience Basic and Clinical 106(2): 110-118. ISSN: 1566-0702.
Abstract: Pancreatic exocrine secretion is known to be facilitated by gastric antral distension via long- and short-route reflexes. In this study, we studied the effects of gastric distension on intra-pancreatic nerve discharges and blood insulin level as well as pancreatic exocrine secretion. Mongrel dogs were anesthetized with ketamine and thiopental, and immediately decerebrated. This study consisted of two series of experiments. In the first series, efferent discharges in an intra-pancreatic nerve branch were recorded, and its responses to antral distension were analyzed. In the second series, effects of antral distension on pancreatic exocrine secretion and blood insulin level were observed before and after vagotomy in splanchnicectomized dogs. Efferent discharges in a pancreatic nerve branch were increased by antral distension. Neither vagotomy nor splanchnicectomy produced obvious changes in the neural response. In splanchnicectomized dogs, antral distension elevated blood insulin level and increased pancreatic exocrine secretion. After subsequent vagotomy, these effects were reduced, but the increases were still greater than 50%. These results indicate that the antro-pancreatic short-route reflex plays a significant role in exocrine secretion, and also suggest that insulin release is increased by antral distension independent of blood glucose level.
Descriptors: endocrine system, chemical coordination and homeostasis, nervous system, neural coordination, splanchnicectomy, experimental surgical techniques, laboratory techniques, vagotomy, antro pancreatic reflexes, gastric distension.

Green, S.L., J.M. Westendorf, H. Jaffe, H.C. Pant, L.C. Cork, E.A. Ostrander, F. Vignaux, and J.E.J. Ferrell (2005). Allelic variants of the canine heavy neurofilament (NFH) subunit and extensive phosphorylation in dogs with motor neuron disease. Journal of Comparative Pathology 132(1): 33-50. ISSN: 0021-9975.
NAL Call Number: 41.8 J82
Abstract: Aberrant accumulation of extensively phosphorylated heavy (high molecular weight) neurofilament (NFH) and neurodegeneration are features of hereditary canine spinal muscular atrophy (HCSMA), an animal model of human motor neuron disease. In this study, the canine NFH gene was mapped, cloned, and sequenced, and electrospray/mass spectrometry was used to evaluate the phosphorylation state of NFH protein from normal dogs and dogs with HCSMA. The canine NFH gene was localized to a region on canine chromosome 26 that corresponds to human NFH on chromosome 22q. The predicted length of the canine NFH protein is 1135 amino acids, and it shares an 80.3% identity with human NFH and >74.6% with murine NFH proteins. Direct sequencing of NFH cDNA from HCSMA dogs revealed no mutations, although cDNA sequence and restriction fragment length polymorphism (RFLP) analysis indicates that there are at least three canine NFH alleles, differing in the position and number (61 or 62) of Lys-Ser-Proline (KSP) motifs. The two longest alleles (L1 and L2), each with 62 KSP repeats, contain an additional 24-base insert and were observed in both normal and HCSMA dogs. However, the shorter allele (the C allele), with 61 KSP sites and lacking the 24-base insertion, was absent in dogs with HCSMA. Mass spectrometry data indicated that almost all of the NFH KSP phosphorylation sites were occupied. No new or extra sites were identified in native NFH purified from the HCSMA dogs. The predominance of the two longest NFH alleles and the additional KSP phosphorylation sites they confer probably account for the presence of extensively phosphorylated NFs detected immunohistochemically in dogs with HCSMA.
Descriptors: animal model, human motor neuron disease, genetics, hereditary canine spinal muscular atrophy (HCSMA), neurodegeneration .
Notes: Library: National-Library-of-Medicine.

Green, S.L., D.M. Bouley, M.J. Pinter, L.C. Cork, and G.T. Vatassery (2001). Canine motor neuron disease: clinicopathologic features and selected indicators of oxidative stress. Journal of Veterinary Internal Medicine 15(2): 112-119. ISSN: 0891-6640.
NAL Call Number: SF601.J65
Abstract: Hereditary canine spinal muscular atrophy (HCSMA) is an inherited motor neuron disease affecting a kindred of Brittanies. We have examined the clinicopathologic abnormalities in 57 animals with HCSMA, including 43 affected adult dogs and 14 homozygote pups. We also measured selected biochemical indices of oxidative stress: serum vitamin E (alpha-tocopherol) and Se concentrations; serum concentrations of Cu, Zn, Mg, and Fe; and total superoxide dismutase and glutathione peroxidase activities in red blood cells. Dogs with HCSMA had the following abnormalities: regenerative anemia, hypoglobulinemia, hypochloremia, and abnormally high creatine kinase and liver alkaline phosphatase activities. Serum Cu concentration was significantly (P = .01) increased in adult dogs with HCSMA compared to control dogs. Serum vitamin E concentrations tended to be lower in adult dogs with HCSMA compared to controls, and were significantly (P = .01) lower in homozygote pups compared to control pups.
Descriptors: veterinary medicine, medical sciences, neural coordination, hereditary canine spinal muscular atrophy, nervous system disease, motor neuron disease, muscle disease, clinicopathologic features, oxidative stress.

Harris, S.B., M.G. Darwin, S.R. Russell, J.M. O'Farrell, M. Fletcher, and B. Wowk (2001). Rapid (0.5 degrees C/min) minimally invasive induction of hypothermia using cold perfluorochemical lung lavage in dogs. Resuscitation 50(2): 189-204. ISSN: 0300-9572.
Abstract: OBJECTIVE: Demonstrate minimally invasive rapid body core and brain cooling in a large animal model. DESIGN: Prospective controlled animal trial. SETTING: Private research laboratory. SUBJECTS: Adult dogs, anesthetized, mechanically ventilated. INTERVENTIONS: Cyclic lung lavage with FC-75 perfluorochemical (PFC) was administered through a dual-lumen endotracheal system in the new technique of 'gas/liquid ventilation' (GLV). In Trial-I, lavage volume (V-lav) was 19 ml/kg, infused and withdrawn over a cycle period (tc) of 37 s. (effective lavage rate V'-lav=31 ml/kg/min.) Five dogs received cold (approximately 4 degrees C) PFC; two controls received isothermic PFC. In Trial-II, five dogs received GLV at V-lav=8.8 ml/kg, tc=16 s, V'-lav=36 ml/kg/min. MEASUREMENTS AND MAIN RESULTS: Trial-I tympanic temperature change was -3.7+/-0.6 degrees C (SD) at 7.5 min, reaching -7.3+/-0.6 degrees C at 18 min. Heat transfer efficiency was 60%. In Trial-II, efficiency fell to 40%, but heat-exchange dead space (VDtherm) remained constant. Lung/blood thermal equilibration half-time was <8 s. Isothermic GLV caused hypercapnia unless gas ventilation was increased. At necropsy after euthanasia (24 h), modest lung injury was seen. CONCLUSIONS: GLV cooling times are comparable to those for cardiopulmonary bypass. Heat and CO(2) removal can be independently controlled by changing the mix of lavage and gas ventilation. Due to VDtherm of approximately 6 ml/kg in dogs, efficient V-lav is >18 ml/kg. GLV cooling power appears more limited by PFC flows than lavage residence times. Concurrent gas ventilation may mitigate heat-diffusion limitations in liquid breathing, perhaps via bubble-induced turbulence.
Descriptors: animal model, minimally invasive, rapid body core, brain cooling, hypothermia .

Horais, K., V. Hruby, S. Rossi, D. Cizkova, C. Meschter, R. Dorr, and T.L. Yaksh (2003). Effects of chronic intrathecal infusion of a variant delta opioid agonist in dogs. Toxicological Sciences 71(2): 263-275. ISSN: 1096-6080.
NAL Call Number: RA1190.F8
Abstract: To define the effects of chronic spinal exposure to a highly selective variant delta opioid agonist c(DPen2,DPen5)enkephalin (DPDPE), adult beagles were prepared with chronic lumbar intrathecal catheters. Groups of dogs received intrathecal infusions (100 mul/h) of saline (vehicle), DPDPE 3 mg/ml or 6 mg/ml for 28 days. Over the 28-day period, saline or 3 mg/ml showed minimal changes in neurological function, whereas in the 6 mg/ml animals, prominent hind limb dysfunction evolved over the 28-day interval. Histopathology in control animals displayed a modest pericatheter reaction considered normal for this model. Dogs receiving DPDPE (three of four at 6 mg/ml and one of four at 3 mg/ml) but not saline (zero of four) developed large inflammatory masses (granulomas) in the intrathecal space located proximal to the catheter tip. In these masses, severe chronic inflammatory changes in combination with necrosis and fibrosis was detected. Occasional focal destruction of neuropil was detected also in the adjacent spinal cord parenchyma. These masses contained extensive accumulation of mouse antihuman macrophages (MAC)-positive inflammatory cells expressing tumor necrosis factor-alpha (TNF-alpha), revealing infiltration of macrophages, granulocytes, and monocytes. In separate animals, prepared with dual intrathecal catheters, lumbar CSF was sampled at specified time points following intrathecal bolus (3 mg/ml) and 24 h DPDPE infusion (3 mg/ml and 6 mg/ml). Steady-state cerebrospinal fluid (CSF) DPDPE levels were 18.6 +- 1.0 and 22.6 +- 4.0 mug/ml for 3 mg/ml and 6 mg/ml infusions respectively. These results indicate that this variant delta opioid agonist DPDPE produces a concentration and time-dependent formation of an intrathecal inflammatory mass.
Descriptors: neural coordination, pharmacology, toxicology, hind limb dysfunction, nervous system disease, toxicity, drug induced, intrathecal granuloma.

Ito, T., T. Nakamura, K. Suzuki, T. Takagi, T. Toba, A. Hagiwara, K. Kihara, T. Miki, H. Yamagishi, and Y. Shimizu (2003). Regeneration of hypogastric nerve using a polyglycolic acid (pga)-collagen nerve conduit filled with collagen sponge proved electrophysiologically in a canine model. International Journal of Artificial Organs 26(3): 245-251. ISSN: 0391-3988.
Abstract: The hypogastric nerve (HGN) is a sympathetic nerve in the peritoneal cavity and controls urinary and seminal functions. In this study, the regeneration of HGN was determined by using a new type of an artificial nerve conduit, polyglycolic acid (PGA)-collagen nerve conduit filled with collagen sponge in two dogs. A PGA-collagen nerve conduit (diameter=2mm) was interposed in a 10 mm gap of the right HGN. The regeneration of the HGN was evaluated electrophysiologically 8 months after the operation. The intraluminal pressure of spermatic duct and the bladder neck were elevated 80 mmHg and 25 mmHg respectively by the stimulation across the regenerated HGN. The prostate contraction was also elicited. The responses diminished after the excision of the regenerated portion of HGN. These results proved the regeneration of HGN and this nerve conduit will be great help for patients who suffer from urinary and seminal disturbances.
Descriptors: nervous system, neural coordination, polyglycolic acid collagen nerve conduit, laboratory equipment.

Juraschko, K., A. Meyer Lindenberg, I. Nolte, and O. Distl (2003). Analysis of systematic effects on congenital sensorineural deafness in german dalmatian dogs. Veterinary Journal 166(2): 164-169. ISSN: 1090-0233.
NAL Call Number: SF601.V484
Abstract: We have analysed the systematic influences, phenotypic colour markers and the additive genetic variation for congenital sensorineural deafness (CSD) in German Dalmatian dogs in order to help elucidate the importance of phenotypic breed characteristics for genetic differences of CSD. Linear animal models using restricted maximum likelihood methods were employed to estimate variance components. Data were obtained from all three German Dalmatian kennel clubs associated with the German Association for Dog Breeding and Husbandry (VDH). CSD was recorded by standardized protocols for brainstem auditory-evoked response (BAER). The material included 1899 German Dalmatian dogs from 354 litters in 169 different kennels. BAER testing results were from the years 1986 to 1999. Pedigree information was available for up to seven generations. The animal model regarded the fixed effects of sex, coat colour, eye colour, presence of patches, litter size, percentage of examined puppies per litter, kennel club, and inbreeding coefficient. The common environment of the litter and kennel as well as the additive genetic effect of the animal were taken into account as randomly distributed effects. The fixed effects of eye colour, percentage of puppies examined per litter and kennel club were significant in the mixed model analysis. A significant proportion of additive genetic variation could be shown despite corrections for phenotypic colour variants. The heritability estimate for CSD in German Dalmatian dogs was h2 = 0.27 +- 0.07. The additive genetic correlation of CSD with presence of blue eyes was rg = 0.53 +- 0.41 and with presence of patches rg = -0.36 +- 0.24. We concluded that additional genes other than those associated with phenotypic colour markers in German Dalmatian dogs significantly contribute to the occurrence of CSD.
Descriptors: molecular genetics, biochemistry and molecular biophysics, nervous system, neural coordination, sense organs, sensory reception, veterinary medicine, medical sciences, congenital sensorineural deafness, CSD, congenital disease, ear disease, nervous system disease, diagnosis, genetics, therapy, german association for dog breeding and animal husbandry, brainstem auditory evoked response, breeding, genetic variation, phenotypic color markers.

Kakiuchi, M., T. Ohashi, K. Tanaka, N. Ohara, K. Kamiyama, K. Morikawa, and H. Kato (1998). Central nervous system effects of the novel antiallergic agent hsr-609 and typical antiallergic agents using behavioral and electroencephalographic analyses in dogs. Japanese Journal of Psychopharmacology 18(5): 189-199. ISSN: 1340-2544.
Abstract: We studied the central nervous system (CNS) effects of 3-(4-(8-fluoro-5, 11-dihydrobenz(b) oxepino(4, 3-b)pyridin-11-ylidene)piperidino)propionic acid dihydrate (HSR-609), a novel amphoteric antiallergic agent having antihistaminic activity. Its effects on gross behavior, spontaneous electroencephalograms (EEG) and some pharmacological parameters of unanesthetized, unrestrained dogs with chronic indwelling brain electrodes after oral administration were compared with typical antiallergic agents and 8-fluoro-5, 11-dihydro-11-(1-methyl-4-piperidylidene)benz(b)oxepino(4,3-b)pyridine (PY-608), a non-amphoteric basic compound having a similar chemical structure to HSR-609. HSR-609 (1, 10 and 100 mg/kg) and terfenadine (100 mg/kg) had no effect on the behavior, EEG patterns, sleep-wakefulness cycles or EEG power spectrum. Cyproheptadine (10 mg/kg), ketotifen (30 mg/kg) and PY-608 (10 mg/kg) increased slow waves with high amplitude in all EEG leads and caused dissociation between the slowing of EEG and waking behavior. Both azelastine (30 mg/kg) and oxatomide (100 mg/kg) caused generalized seizure discharges accompanied by agitation with the former and sedation with the latter. These findings suggest that observations of behavior and EEG in conscious dogs can be useful for clarifying the pharmacological characteristics of various antiallergic agents on the CNS. We were able to show that HSR-609 has no effect on the behavior and EEG of dogs because of its amphoteric chemical structure.
Descriptors: behavior, nervous system, neural coordination, pharmacology, electroencephalography, monitoring method.

Kakkis, E., M. Passage, P. Belichenko, M. Mcentee, C. Le S Vogler, R. Esquivel, and W. Mobley (2003). Effective reduction of lysosomal storage in brain and meninges following intrathecal administration of iduronidase in canine mucopolysaccharidosis i (mps i). Journal of Inherited Metabolic Disease 26(Supplement 2): 141. ISSN: 0141-8955.
NAL Call Number: RC627.8.J68
Descriptors: metabolism, nervous system, neural coordination, canine mucopolysaccharidosis I, connective tissue disease, genetic disease, metabolic disease, therapy, enzyme replacement therapy, clinical techniques, therapeutic and prophylactic techniques

Kaluzienski, M. (2000). Partial paralysis and altered behavior in dogs treated with melaleuca oil. Journal of Toxicology Clinical Toxicology 38(5): 518-519. ISSN: 0731-3810.
NAL Call Number: RA1190.C5
Descriptors: biochemistry and molecular biophysics, veterinary medicine, medical sciences, toxicology, altered behavior, partial paralysis, meeting abstract

Kangasniemi, M., R.J. Stafford, R.E. Price, E.F. Jackson, and J.D. Hazle (2003). Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors. Investigative Radiology 38(2): 102-107. ISSN: 0020-9996.
Abstract: RATIONALE AND OBJECTIVES: Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. MATERIALS AND METHODS: Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. RESULTS: Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. CONCLUSION: Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE -dynamic MRI.
Descriptors: nervous system, neural coordination, pharmacology, tumor biology, cerebral thermal necrosis, nervous system disease, intracerebral transmissible venereal tumor, neoplastic disease, radiotherapy, contrast enhanced dynamic magnetic resonance imaging, clinical techniques, diagnostic techniques, imaging and microscopy techniques, fast spin echo t1 weighted imaging, sigmoidal exponential model, mathematical and computer techniques, thermal coagulation therapy, therapeutic and prophylactic techniques, reactive thermal change.

Lamouche, S. and N. Yamaguchi (2003). Pacap release from the canine adrenal gland in vivo: its functional role in severe hypotension. American Journal of Physiology 284(2 Part 2): R588-R597. ISSN: 0002-9513.
NAL Call Number: 447.8 Am3
Abstract: This study was to investigate if endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) can be released during direct splanchnic nerve stimulation in vivo and to determine whether PACAP in the adrenal gland can modulate the medullary response to sympathoadrenal reflex. The output of adrenal catecholamine and PACAP-38-like immunoreactivity (PACAP-38-ir) increased in a frequency-dependent manner after direct splanchnic nerve stimulation (0.2-20 Hz). Both responses were highly reproducible, and PACAP-38-ir output closely correlated with catecholamine output. Sodium nitroprusside (SNP; 0.1 mg/kg iv bolus) caused a severe hypotension resulting in marked increases in catecholamine secretion. In the presence of local PACAP-27 (125 ng), the maximum catecholamine response to SNP was significantly potentiated in a synergistic manner compared with that obtained in the group receiving SNP or PACAP-27 alone. The study indicates that endogenous PACAP-38 can be released particularly when the sympathoadrenal system is highly activated and that the local exogenous PACAP-27 enhanced the reflex-induced catecholamine release, suggesting collectively a facilitating role of PACAP as neuromodulator in the sympathoadrenal function in vivo.
Descriptors: endocrine system, chemical coordination and homeostasis, nervous system, neural coordination, hypotension,vascular disease, sympathoadrenal reflex.

Leonard, S.E. and R. Kirby (2002). The role of glutamate, calcium and magnesium in secondary brain injury. Journal of Veterinary Emergency and Critical Care 12(1): 17-32. ISSN: 1534-6935.
NAL Call Number: SF778.J68
Abstract: Objective: To review the roles that glutamate, calcium and magnesium play in both normal brain function and in the events following traumatic brain injury. Human data synthesis: Elevated extracellular brain glutamate levels have been well documented in humans following traumatic brain injury. Therapies focusing on glutamate receptor antagonists have not yet been shown to have clinical effectiveness significant enough to outweigh the side effects. Newer strategies are currently being explored focusing on the many secondary cellular cascades interacting to culminate in cell injury and death. Veterinary data synthesis: Derangements in glutamate, calcium and magnesium have been well documented in animals following traumatic brain injury. Research studies using animal models other than small laboratory animals such as rats, mice and rabbits are very limited. Prospective veterinary clinical trials in dogs and cats are needed to determine the potential success that various therapeutic strategies might have in the field of small animal emergency and critical care medicine. Conclusions: Alterations in the levels of glutamate, calcium and magnesium play a critical role in secondary brain injury. The future development of clinically-tolerated and effective antagonists of glutamate, glutamate receptors, and other downstream mediators has the potential to revolutionize the therapy of traumatic brain injured patients.
Descriptors: animal health, brain, calcium, glutamates, glutamic acid, intensive care, magnesium, therapy, trauma, cats, dogs.

Lian, X.Y. and J.L. Stringer (2004). Inhibition of aconitase in astrocytes increases the sensitivity to chemical convulsants. Epilepsy Research 60(1): 41-52. ISSN: 0920-1211.
Descriptors: behavior, nervous system, neural coordination, pharmacology, epilepsy, nervous system disease, neuronal damage, injury, nervous system disease, seizure, wet dog shakes, nervous system disease, drug induced, etiology, pathology, immunohistochemistry, immunologic techniques, laboratory techniques, silver staining, genetic techniques, chemical convulsant sensitivity.

Macdonald, R.L., L.S. Marton, P.K. Andrus, E.D. Hall, L. Johns, and M. Sajdak (2004). Time course of production of hydroxyl free radical after subarachnoid hemorrhage in dogs. Life Sciences 75(8): 979-989. ISSN: 0024-3205.
NAL Call Number: Q2.C6
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, nervous system, neural coordination, subarachnoid hemorrhage, nervous system disease, vascular disease, vasospasm, lipid peroxidation.

Mealey, K.L., S. Greene, R. Bagley, J. Gay, R. Tucker, P. Gavin, K. Schmidt, and F. Nelson (2008). P-glycoprotein contributes to the blood-brain, but not blood-cerebrospinal fluid, barrier in a spontaneous canine p-glycoprotein knockout model. Drug Metabolism and Disposition the Biological Fate of Chemicals 36(6): 1073-9.
NAL Call Number: RM300.A1D7
Abstract: P-glycoprotein is considered to be a major factor impeding effective drug therapy for many diseases of the central nervous system (CNS). Thus, efforts are being made to gain a better understanding of P-glycoprotein's role in drug distribution to brain parenchyma and cerebrospinal fluid (CSF). The goal of this study was to validate and introduce a novel P-glycoprotein-deficient (ABCB1-1Delta) canine model for studying P-glycoprotein-mediated effects of drug distribution to brain tissue and CSF. CSF concentrations of drug are often used to correlate efficacy of CNS drug therapy as a surrogate for determining drug concentration in brain tissue. A secondary goal of this study was to investigate the validity of using CSF concentrations of P-glycoprotein substrates to predict brain tissue concentrations. Loperamide, an opioid that is excluded from the brain by P-glycoprotein, was used to confirm a P-glycoprotein-null phenotype in the dog model. ABCB1-1Delta dogs experienced CNS depression following loperamide administration, whereas ABCB1 wild-type dogs experienced no CNS depression. In summary, we have validated a novel P-glycoprotein-deficient canine model and have used the model to investigate transport of the P-glycoprotein substrate (99m)Tc-sestamibi at the blood-brain barrier and blood-CSF barrier.
Descriptors: blood brain barrier metabolism, central nervous system depressants pharmacology, loperamide pharmacology, models, animal, p glycoprotein genetics, technetium tc 99m sestamibi cerebrospinal fluid, brain metabolism, dogs, technetium tc 99m sestamibi pharmacokinetics.

Miklosi, A., J. Topal, and V. Csanyi (2007). Big thoughts in small brains? Dogs as a model for understanding human social cognition. Neuroreport 18(5): 467-71. ISSN: 0959-4965.
Abstract: In this review we argued that dogs can provide a good model for both the evolution of human social-cognitive abilities and studying the underlying neural and genetic structures of these behavioural features. The key difference between the present and other approaches for modelling human social evolution lies in the assumption that there is a large overlap between the human and dog behaviour complex because during their evolution in close contact with human groups dogs evolved functionally similar social skills. Thus the parallel investigation of the human and dog behaviour complex widens our possibility for understanding human social cognition because it allows the modelling of the interaction between various components in contrast to other models which are often restricted to modelling a single aspect of human social cognitive skills.
Descriptors: brain physiology, cognition physiology, evolution, social behavior, brain anatomy and histology, dogs, models, animal.

Milgram, N.W. (2003). Cognitive experience and its effect on age dependent cognitive decline in beagle dogs. Neurochemical Research 28(11): 1677-1682. ISSN: 0364-3190.
NAL Call Number: QP356.3 .N457
Abstract: Test-sophisticated beagle dogs show marked age sensitivity in a size discrimination learning task, with old and senior dogs performing significantly more poorly than young dogs. By contrast, age differences in learning were not seen in dogs naive with respect to neuropsychological test experience. These results indicate that old animals benefit less from prior cognitive experience than young animals, which is an example of an age-dependent loss in plasticity. This finding also suggests that behaviorally experienced animals are a more useful model of human cognitive aging than behaviorally naive animals. We also looked at the effect of a program of behavioral enrichment in aged dogs. One year of enrichment did not lead to significant differences, but after 2 years the behaviorally enriched group performed significantly better than the control group. The effect after 2 years indicates that a prolonged program of cognitive enrichment can serve as an effective intervention in aged dogs. These findings demonstrate that cognitive abilities in aged animals can be modified by providing behavioral experience, indicating that cognitive abilities remain moderately plastic, even in very old animals.
Descriptors: beagle, breed, age effects,cognition,neuropsychological tests,age-dependedn loss in plasticity,behavioral enrichment, length of enrichment program.

Monaco, B.A., A. Benicio, I.S. Contreras, L.E. Mingrone, G. Ballester, and L.F. Moreira (2007). Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach. Arquivos Brasileiros De Cardiologia 88(3): 291-6.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES: To evaluate the effectiveness of acute ischemic preconditioning (IP), based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal cord protection and to asses SSEP importance in spinal cord neuromonitoring. METHODS: Twenty-eight dogs were submitted to spinal cord ischemic injury attained by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross-clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group that was previously submitted to IP. The IP cycles were determined based on SSEP changes. RESULTS: Tarlov scores of the IP groups were significantly better than those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and in 6 from C60 group, although all dogs from IP45 group were neurologically normal, as 4 dogs from IP60. There was a significant correlation between SSEP recovery time until one hour of aortic reperfusion and the neurological status (p = 0.011), showing sensitivity of 75% and specificity of 83%. CONCLUSION: Repetitive acute IP based on SSEP is a protection factor during spinal cord ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good neurological injury assessment method during surgical procedures that involve spinal cord ischemia.
Descriptors: aorta, thoracic surgery, evoked potentials, somatosensory physiology, ischemic preconditioning standards, spinal cord ischemia diagnosis, spinal cord ischemia prevention and control, analysis of variance, dogs, ischemic preconditioning methods, models, animal, monitoring, intraoperative methods, paraplegia etiology, reperfusion methods, sensitivity and specificity, spinal cord blood supply, spinal cord physiopathology, spinal cord ischemia etiology, spinal cord ischemia physiopathology, statistics, nonparametric, time factors, vascular surgical procedures adverse effects.
Language of Text: ; Portuguese; Non-.

Naito, M., X.P. Yang, and S. Chiba (2004). Modification of transmitter release from periarterial nerve terminals by dipyridamole in canine isolated splenic artery. Clinical and Experimental Pharmacology and Physiology 31(3): 185-189. ISSN: 0305-1870.
Abstract: 1. The aim of the present study was to determine the modulatory effects of dipyridamole on purinergic and adrenergic transmission in the canine isolated, perfused splenic artery. 2. Periarterial nerve electrical stimulation readily induced a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X receptor-mediated constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated response. 3. Exposure of tissues to dipyridamole (0.1-1 mumol/L) dose-dependently inhibited both the first and second peaks of the vasoconstrictor response at a low frequency of stimulation (1 Hz), whereas at an intermediate frequency of stimulation (4 Hz), the first peak of the response was depressed without any significant effect being observed on the second peak of constriction. 4. At a higher dose (1 mumol/L) dipyridamole potentiated vasoconstrictor responses to noradrenaline (0.03-1 nmol). At any doses used, dipyridamole had no effect on the vasoconstrictor responses to ATP (0.03-1 mumol). 5. Tyramine (0.01-0.3 mumol) induced vasoconstriction in a dose-dependent manner. The dose-response curves for tyramine were shifted to the right following treatment with dipyridamole (0.1-1 mumol/L). 6. The present results indicate that dipyridamole may inhibit purinegic and adrenergic transmission presynaptically, whereas postsynaptically dipyridamole may potentiate the adrenergic vascular constriction by inhibition of transmitter uptake.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, cotransmission, neuronal vasoconstrictor response, transmitter release modification.

Nolan, E.R., M.B. Bailie, and N.B. Olivier (2008). Effect of autonomic blockade on ventricular repolarization shortening: response to behavioral stimulus in paced dogs. Autonomic Neuroscience Basic and Clinical 140(1-2): 66-71. ISSN: 1566-0702.
Abstract: Autonomic tone has been suggested to be a significant determinant of ventricular repolarization duration with both rate dependent and independent effects. Using the His bundle-paced dog, a model that eliminates the need for QT correction factors, we explored the rate-independent effects of sympathetic and parasympathetic blockade on ventricular repolarization shortening following an excitatory stimulus. Six male His bundle-paced beagle dogs were paced at 80 bpm and fitted with jackets, surface ECG electrodes, and radiotelemeters. Dogs were given propranolol, atropine methyl nitrate, or the appropriate control in a four-period crossover design. Doses were based on literature reviews and unpublished pharmacokinetic/pharmacodynamic modeling to provide efficacious beta- and parasympathetic blockade throughout the data collection period. Data collection began at 11 am and concluded at 11 am the following day, with event stimuli provided by investigators entering the room at 5 pm and at 7 am the following morning. One minute of ECG data were sampled every 15 min and these means were averaged to generate hourly means for the 24 hour data collection period. Treatment with atropine attenuated RT interval shortening when compared with the vehicle group at both the 5 pm and 7 am stimulus. In contrast, propranolol was not associated with significant effects on RT interval duration at either time point. These results suggest that parasympathetic withdrawal is the primary factor responsible during both awake hours (5 pm) and in the transition from deep sleep to the awake state (7 am) in the facilitation of RT interval shortening following an excitatory stimulus. The attenuation of RT interval shortening following atropine treatment may be a direct effect, or an indirect effect requiring an excited state to become evident. The use of a model that eliminates the need to apply correction factors to repolarization indices helps to clarify the role of the autonomic nervous system on ventricular repolarization.
Descriptors: autonomic nervous system physiology, heart innervation, heart physiology, heart rate physiology, heart ventricles innervation, ventricular function, adrenergic beta antagonists pharmacology, atropine pharmacology, autonomic nervous system drug effects, biological clocks drug effects, biological clocks physiology, bundle of his drug effects, bundle of his physiology, circadian rhythm physiology, dogs, electric stimulation, electrocardiography drug effects, heart rate drug effects, membrane potentials drug effects, membrane potentials physiology, models, animal, muscarinic antagonists pharmacology, pacemaker, artificial, parasympathetic nervous system drug effects, parasympathetic nervous system physiology, propranolol pharmacology, sympathetic nervous system drug effects, sympathetic nervous system physiology, time factors.

Qureshi, A.I., M.F. Suri, A.J. Ringer, L.R. Guterman, and L.N. Hopkins (2002). Regional intraparenchymal pressure differences in experimental intracerebral hemorrhage: effect of hypertonic saline. Critical Care Medicine. 30(2): 435-41. ISSN: 0090-3493.
Abstract: OBJECTIVE: To study regional intraparenchymal pressures within the cranial cavity during and after formation of intracerebral hemorrhage. We also assessed the effect of hypertonic saline on intraparenchymal pressure in different brain regions and on regional brain distribution of sodium within the brain. DESIGN: Prospective, controlled, laboratory trial. SETTINGS: Animal research laboratory. SUBJECTS: Eight mongrel dogs, weighing 15-25 kg. INTERVENTION: We introduced an intracerebral hematoma in eight mongrel dogs by infusing 6 mL of autologous arterial blood in the deep white matter adjacent to the basal ganglia. Sodium chloride (23.4%, 1.4 mL/kg) then was administered intravenously 6 hrs after introduction of hematoma. MEASUREMENTS AND MAIN RESULTS: Parenchymal pressure monitors were placed in the perihematoma region, both frontal lobes, and the cerebellum to record intraparenchymal pressure during and 6 hrs after intracerebral hematoma formation. Intraparenchymal pressure measurements were recorded for 3 more hours after administration of 23.4% sodium chloride. Regional cerebral perfusion pressure was calculated for each intraparenchymal pressure measurement. Regional sodium distribution was measured in extracts from brain regions by using ion selective electrode technique. A higher elevation in intraparenchymal pressure was recorded in the perihematoma region during the introduction of the hematoma compared with other compartments. After 5 mL of autologous blood was introduced, intraparenchymal pressure (mm Hg +/- SE) was significantly higher in the perihematoma region (42.1 +/- 3.5) than in the ipsilateral (30.0 +/- 4.6, p <.05) and contralateral (27.1 +/- 5.5, p <.01) frontal lobes and cerebellum (29.1 +/- 4.5, p <.05). Four hours after introduction of the hematoma, the cerebral perfusion pressure recorded in the perihematoma region (43.6 +/- 9.7) remained significantly lower than in the ipsilateral (58.6 +/- 9.3, p <.05) but not the contralateral frontal lobes (54.7 +/- 10.1) and cerebellum (51.0 +/- 11.1). Administration of 23.4% sodium chloride immediately reduced intraparenchymal pressure in each compartment. This effect was still observed at 3 hrs in each compartment. Sodium concentration was higher in the perihematoma region than in the frontal lobes, cerebellum, or brain stem. CONCLUSIONS: Prominent differences were observed in intraparenchymal pressure and cerebral perfusion pressure in the perihematoma region and frontal lobes during and after intracerebral hematoma. We speculate that the potential importance of regional intraparenchymal pressure differences in the clinical settings may be under appreciated. In this canine model of intracerebral hematoma, a single dose of hypertonic saline effectively reduces the intraparenchymal pressure in all regions of the brain.
Descriptors: animal model, mongrel dogs, regional intraparenchymal pressure, intracerebral hemorrhage, hypertonic saline.

Ridgway, P., T.E. Nixon, and J.P. Leach (2003). Occupational exposure to organic solvents and long-term nervous system damage detectable by brain imaging, neurophysiology or histopathology. Food and Chemical Toxicology 41(2): 153-187. ISSN: 0278-6915.
NAL Call Number: 391.8 F73
Abstract: The purpose of the present review is to assess the evidence published in scientific literature that industrial organic solvents as a generic group have the ability to induce long-term nervous system damage in workers that can be detected by techniques other than neuropsychological testing. The main body of evidence considered in this review was 40 studies involving the use of brain imaging, neurophysiological testing, gross autopsy or histopathology in groups of workers with long-term solvent exposure. Case reports involving both solvent abuse and occupational exposure, and experimental animal data have also been reviewed as supporting data. A number of the studies in groups of workers provide evidence of the presence of marginal atrophic abnormalities in the brain or deficits in nerve conduction velocity in solvent-exposed workers. However, there are limitations in the design of many of these studies, the strength of association between exposure and effect is not consistently strong, no dose-response relationship can be detected, the reported changes lack specificity and there is no coherence between the human and experimental animal data. Overall, it is not possible to draw reliable conclusions with respect to the presence or absence of nervous system damage related to the common properties of organic solvents.
Descriptors: nervous system, neural coordination, toxicology, organic solvent abuse, brain imaging, imaging, microscopy techniques, laboratory techniques, gross autopsy, histopathology, cytology techniques .

Rozman, J. and S. Ribaric (2007). Selective recording of electroneurograms from the left vagus nerve of a dog during stimulation of cardiovascular or respiratory systems. Chinese Journal of Physiology 50(5): 240-50. ISSN: 0304-4920.
Abstract: Selective electroneurograms (ENGs) from superficial regions of the left vagus nerve of a dog were recorded with a 33-electrode spiral cuff (cuff) implanted on the nerve at the neck in an adult Beagle dog. The electrodes in the cuff were arranged in thirteen groups of three electrodes (GTE 1-13). To identify the relative positions of the particular nerve regions that innervated the heart and lungs, stimulating pulses (2 mA, 200 micros, 20 Hz) were individually delivered to all thirteen GTEs. It was shown that by delivering stimulating pulses to GTEs 4 and 9, heart rate, blood pressure and respiratory rate were modulated. Precisely, only when the stimuli were delivered to GTE 9, the heart rate began to fall and only when the stimuli were delivered to GTE 4 the rate of breathing decreased. To test the selectivity of recording the above-defined groups GTEs 4 and 9 and randomly chosen GTEs 1 and 7 were simultaneously used as recording GTEs while cardio-vascular or respiratory systems were stimulated by carotid artery compression, epinephrine injection and non-invasive, positive end-pressure ventilation. Results showed that stimulations elicited site-specific changes in ENG power spectra recorded from the superficial regions of the vagus nerve. Power spectrum of the ENG recorded with GTE 9, contained frequencies belonging to the neural activity elicited by compression of the carotid artery and injection of epinephrine. The power spectrum of the ENG recorded with GTE 4, contained frequencies belonging to the neural activity elicited by non-invasive, positive end-expiratory pressure ventilation. We concluded that the multi-electrode nerve cuff enables selective stimulation and recording of nerve activity from internal organs.
Descriptors: cardiovascular system drug effects, electrodiagnosis instrumentation, electrodiagnosis methods, respiratory system drug effects, vagus nerve physiology, blood pressure drug effects, dogs, electric impedance, electric stimulation, electrodes, electrophysiology, epinephrine pharmacology, heart rate drug effects, models, animal, sensitivity and specificity, vagus nerve anatomy and histology.

Schaefer, G.J., D.T. Kirkpatrick, J.F. Holson, C.P. Chengelis, K.S. Regan, and V.J. Piccirillo (2003). A six-week inhalation neurotoxicity study of methyl bromide in dogs. Toxicological Sciences 72(S-1): 304 ISSN: 1096-6080.
NAL Call Number: RA1190.F8
Descriptors: nervous system, neural coordination, toxicology, locomotor activity.

Sharifov, O.F., V.V. Fedorov, G.G. Beloshapko, A.V. Glukhov, A.V. Yushmanova, and L.V. Rosenshtraukh (2004). Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs. Journal of the American College of Cardiology 43(3): 483-490. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES We studied the effects of beta-adrenergic and cholinergic stimulation and blockade on spontaneous atrial fibrillation (AF) in the intact dog heart. BACKGROUND Paroxysmal AF is often preceded by changes in autonomic tone, but the relative roles of adrenergic and cholinergic influences on AF induction are not well known. METHODS Perfusion of catecholamines and acetylcholine (ACh), as well as their combination, through the sinus node artery was used to induce AF in 20 anesthetized open-chest dogs without electrical stimulation of atria. RESULTS Isoproterenol and adrenaline (10 to 100 mumol/l) induced AF in 21% (3 of 14) and 17% (1 of 6) of dogs, respectively. Atropine (1 to 2 mg) treatment prevented catecholamine-mediated AF, indicating a critical role of cholinergic tone in these AF episodes. Acetylcholine (2.8 +- 0.3 mumol/l) induced AF in all dogs. Beta-blockade by propranolol (1 mg/kg) did not prevent ACh-induced AF, but increased the threshold ACh concentration for AF induction to 23.5 +- 3.4 mumol/l (p < 0.05). Acetylcholine-mediated AF was facilitated by isoproterenol (1 to 2 and 10 mumol/l), which decreased the threshold ACh concentration for AF induction to 0.5 +- 0.1 and 0.4 +- 0.1 mumol/l, respectively (p < 0.05) and increased the AF duration (from 25 +- 7 to 141 +- 54 and 233 +- 60 s, respectively; p < 0.05). Epicardial mapping of the right atrium (112 unipolar electrodes) demonstrated similar activation patterns during arrhythmias induced by ACh and catecholamines. CONCLUSIONS These data indicate that although both autonomic systems play a role in AF, cholinergic stimulation is likely the main factor for spontaneous AF initiation in this animal model. Adrenergic tone modulates the initiation and maintenance of cholinergically mediated AF.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, pharmacology, spontaneous atrial fibrillation, heart disease, adrenergic stimulation, cholinergic stimulation.

Shelton, G.D., M. Podell, L. Poncelet, S. Schatzberg, E. Patterson, H.C. Powell, and A.P. Mizisin (2003). Inherited polyneuropathy in leonberger dogs: a mixed or intermediate form of charcot-marie-tooth disease? Muscle and Nerve 27(4): 471-477. ISSN: 0148-639X.
Abstract: A spontaneous distal, symmetrical polyneuropathy in related Leonberger dogs with onset between 1 to 9 years of age was characterized clinically, electrophysiologically, histologically, and morphometrically. Exercise intolerance and weakness was associated with a high-steppage pelvic-limb gait, a loss or change in the pitch of the bark, and dyspnea. Neurological examination revealed marked atrophy of the distal limb muscles, depressed spinal and cranial nerve reflexes, and weak or absent movement of the laryngeal and pharyngeal muscles. Electrophysiological evaluation was consistent with denervation and was characterized by loss or marked attenuation of compound muscle action potentials and slowed motor nerve conduction velocity. Muscle biopsy specimens showed neurogenic atrophy. Chronic nerve fiber loss associated with decreased myelinated fiber density and a shift of the axonal size-frequency distribution toward smaller fibers was the predominant finding in peripheral nerve specimens. Pedigree analysis of a large multigenerational family, including nine sibships with at least one affected individual, suggested X-linked inheritance. Mutational and linkage analysis of this family may aid in identification of the chromosomal loci and gene responsible for this inherited axonal neuropathy. Further characterization of this inherited axonal neuropathy may establish the Leonberger dog as a spontaneous animal model of inherited axonal neuropathy and possibly lead to the discovery of a new gene or genes associated with axonal variants.
Descriptors: molecular genetics, biochemistry and molecular biophysics, nervous system, neural coordination, Charcot Marie tooth disease, congenital disease, genetic disease, muscle disease, nervous system disease, chronic nerve fiber loss, distal limb muscle atrophy, dyspnea, respiratory system disease, exercise intolerance, inherited polyneuropathy, genetic disease, muscle weakness, neurogenic atrophy, cranial nerve reflex, motor nerve conduction velocity, myelinated fiber density, spinal nerve reflex.

Siwak, C.T., P. Gruet, F. Woehrle, B.A. Muggenburg, H.L. Murphey, and N.W. Milgram (2000). Comparison of the effects of adrafinil, propentofylline, and nicergoline on behavior in aged dogs. American Journal of Veterinary Research 61(11): 1410-1414. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Descriptors: dogs, age differences, animal behavior, efficacy, mental disorders, drug therapy, quality of life, movement, dosage, pharmacodynamics.
Notes: Includes references.

Siwak, C.T., P.D. Tapp, H.J. Lee, and N.W. Milgram (2000). Age-associated changes in noncognitive behaviors in a canine model of aging. Society for Neuroscience Abstracts 26(1-2): Abstract No. 873.3. ISSN: 0190-5295.
NAL Call Number: QP351.S6
Abstract: Locomotor activity and exploration, which depend on the brain's motor system, are typically viewed independently from cognition. While this may be justified in the case of locomotion, exploration involves sensory processing, investigation, responding to novel stimuli, and information gathering - all of which depend on cognitive processes. To better understand cognitive changes associated with aging, we have developed a number of spontaneous behavior tests, including tests of exploration. Our curiosity test consists of placing a number of novel objects in the test arena and allowing the dog to explore the objects. In this test young dogs show significantly more exploration and contact with novel objects than old dogs. In the model dog test, dogs are placed in an arena with a life-size plastic dog. Young dogs again show significantly more investigative sniffing than old dogs. Young dogs spend significantly more time in contact with a human sitting in the middle of the arena than old dogs. These tests can also distinguish cognitively impaired aged dogs from successful agers. Compared to successful agers, age-impaired dogs spend less time interacting with novel objects, less time interacting with humans, and more time reacting to their reflection in a mirror. These results indicate that aging can affect curiosity, exploration and responses to novelty rather than locomotor activity per se.
Descriptors: aging, nervous system, neural coordination, arena, laboratory equipment, behavior test, analytical method, life size plastic dog, equipment, model dog test, analytical method, age associated changes noncognitive behavior changes, investigative sniffing, mirror, meeting abstract

Siwak, C.T., P. Gruet, F. Woehrle, B.A. Muggenburg, H.L. Murphey, and N.W. Milgram (2000). Comparison of the effects of adrafinil, propentofylline, and nicergoline on behavior in aged dogs. American Journal of Veterinary Research 61(11): 1410-1414. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Abstract: Objective-To compare the efficacy of adrafinil, propentofylline, and nicergoline for enhancing behavior of aged dogs. Animals-36 Beagles between 9 and 16 years old. Procedure-Dogs were randomly assigned to receive adrafinil (20 mg/kg of body weight, PO, q 24 h; n = 12), propentofylline (5 mg/kg, PO, q 12 h; 12), or nicergoline (0.5 mg/kg, PO, q 24 h; 12) for 33 days. Baseline behaviors in an open field and in kennels (home cage) were recorded before treatment. After treatment, behaviors in the open field were recorded 2 hours after drug administration on days 2, 15, and 28, and 10 hours after administration on days 7, 20, and 33. Behaviors in the home cage were recorded 2 and 7 hours after drug administration on days 4, 17, and 30. Results-Treatment with adrafinil resulted in a significant increase in locomotion in each of the open-field tests and an increase in locomotion in the home cage. This latter increase was smaller and more variable than that in the open field. Locomotion was not affected by treatment with propentofylline or nicergoline. In the open field, sniffing decreased over time in all 3 groups, but the largest decline was observed in the propentofylline group. Conclusions and Clinical Relevance-Treatment with adrafinil may improve the quality of life of aged dogs by increasing exploratory behavior and alertness.
Descriptors: behavior, veterinary medicine, medical sciences, nervous system, neural coordination, pharmacology, alertness, exploratory behavior, locomotion, quality of life.

Siwak, C.T., P.D. Tapp, and N.W. Milgram (2001). Effect of age and level of cognitive function on spontaneous and exploratory behaviors in the beagle dog. Learning and Memory 8(6): 317-325. ISSN: 1072-0502.
Abstract: Cognitively characterized young and aged beagle dogs were administered six different spontaneous behavior tests, which provided measures of locomotion, exploration, and social interaction. Consistent with our previous findings, we obtained no overall effect of age on locomotion. We did find, however, that for the aged dogs locomotion correlated with level of cognitive function, being lowest in age-unimpaired dogs and highest in impaired dogs. Exploratory behavior, as measured by response to novelty, varied with age, with young dogs scoring the highest. Young dogs spent more time with novel toys and a person, responded more to a silhouette of a dog, and interacted more with a model dog compared to aged dogs. Among the aged dogs, age-unimpaired dogs spent the greatest amount of time sitting or standing beside a person whereas age-impaired dogs spent the most time reacting to a reflection in a mirror. The age-impaired dogs show undirected, stereotypical types of behavioral patterns. These differences in activity patterns may be linked to underlying age-associated neuropathology.
Descriptors: aging, behavior, nervous system, neural coordination, spontaneous behavior test, assessment method, experimental method, age effects, age associated neuropathology, cognitive function, level, exploration, exploratory behavior, locomotion, social interaction, spontaneous behavior.

Siwak, C.T., P.D. Tapp, S.C. Zicker, H.L. Murphey, B.A. Muggenburg, E. Head, C.W. Cotman, and N.W. Milgram (2003). Locomotor activity rhythms in dogs vary with age and cognitive status. Behavioral Neuroscience 117(4): 813-824. ISSN: 0735-7044.
NAL Call Number: QP351.B45
Abstract: Beagle dogs exhibited diurnal patterns of locomotor activity that varied as a function of age, cognitive status, and housing environment. Aged dogs housed in an indoor facility showed a delayed onset of activity following lights on and displayed shorter bouts of activity, with more rest periods during the day, compared with young dogs. Cognitively impaired aged dogs were more active and showed a delayed peak of activity compared with unimpaired aged dogs. Housing in continuous light did not disrupt activity rhythms. The effect of age was less prominent in dogs housed in an indoor/outdoor facility. This suggests that bright sunlight and natural light-dark transitions are better able to consolidate and synchronize the activity rhythms of the dogs.
Descriptors: behavior, biosynchronization, nervous system, neural coordination, locomotor activity, age related rhythm variation, cognitive status related rhythm variation, diurnal rhythms.

Swissa, M., S. Zhou, I. Gonzalez Gomez, C.M. Chang, A.C. Lai, A.W. Cates, M.C. Fishbein, H.S. Karagueuzian, P.S. Chen, and L.S. Chen (2004). Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death. Journal of the American College of Cardiology 43(5): 858-864. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES: We sought to develop a high-yield canine model of sudden cardiac death (SCD). BACKGROUND: Because electrical stimulation is a powerful means to elicit nerve sprouting, we hypothesize that subthreshold electrical stimulation is more effective than nerve growth factor (NGF) infusion in inducing nerve sprouting and SCD in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). METHODS: We gave subthreshold electrical stimulation to the left stellate ganglion (LSG) in six normal dogs for 41+-9 days (protocol 1) and to six dogs with MI and CAVB for 41+-29 days, while continuously monitoring their cardiac rhythm (protocol 2). We also monitored the rhythm of two dogs with MI, CAVB, and NGF infusion to the LSG and determined the ventricular nerve density in six healthy control dogs. RESULTS: In protocol 1, the hearts from dogs with LSG electrical stimulation had a higher density of nerve fibers immunopositive to tyrosine hydroxylase, synaptophysin, and growth-associated protein-43 than those of normal control dogs (p<0.01). In protocol 2, there was a high magnitude of cardiac nerve sprouting in all dogs studied. Ventricular tachycardia gtoreq8 beats and gtoreq20 beats was more frequent in dogs with electrical stimulation than in dogs with NGF infusion to the LSG (36+-60 and 11+-17 vs. 4.7+-6.1 and 0.1+-0.33 episodes per day, p<0.05 and p<0.03, respectively). Four of six dogs in protocol 2 had SCD. CONCLUSIONS: Subthreshold electrical stimulation of the LSG induces cardiac nerve sprouting and sympathetic hyperinnervation and facilitates the development of a high-yield canine model of ventricular arrhythmia and SCD.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, complete atrioventricular block, heart disease, therapy, myocardial infarction, heart disease, vascular disease, therapy, sudden cardiac death, long term subthreshold electrical stimulation, clinical techniques, therapeutic and prophylactic techniques.

Syuu, Y., H. Matsubara, T. Kiyooka, S. Hosogi, S. Mohri, J. Araki, T. Ohe, and H. Suga (2001). Cardiovascular beneficial effects of electroacupuncture at Neiguan (PC-6) acupoint in anesthetized open-chest dog. Japanese Journal of Physiology 51(2): 231-8. ISSN: 0021-521X.
NAL Call Number: QP34.5.J3
Abstract: Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (p<0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.
Descriptors: animal model, Neiguan electroacupuncture, traditional acupoints, cardiovascular function, pentobarbital, fentanyl,anesthesia, left ventricular (LV) pressure-volume (P-V) data, micromanometer catheter, mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, end-systolic pressure.

Thomsen, M.B., P.G.A. Volders, M. Stengl, R.L. Spatjens, J.D.M. Beekman, U. Bischoff, M.A. Kall, K. Frederiksen, J. Matz, and M.A. Vos (2003). Electrophysiological safety of sertindole in dogs with normal and remodeled hearts. Journal of Pharmacology and Experimental Therapeutics 307(2): 776-784. ISSN: 0022-3565.
NAL Call Number: 396.8 J82
Abstract: Inhibition of the potassium current IKr and QT prolongation are associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. We investigated the cardiac electrophysiological effects of sertindole, an antipsychotic drug reported to prolong the QT interval in schizophrenic patients. In cell cultures, sertindole seemed to be a selective blocker of IHERG over other ion currents. For IHERG, the IC50 value was 64 +- 7 nM, whereas ISCN5A, ICa,L, ICa,T, IKCNQ1/KCNE1, and IKv4.3 were blocked in the micromolar range. In canine ventricular myocytes, the IC50 value for IKr inhibition by sertindole was 107 +- 21 nM. Action potentials in these cells prolonged in a reverse rate- and concentration-dependent manner at 10 to 300 nM sertindole. In vivo, sertindole was administered to anesthetized dogs at clinically relevant (0.05-0.20 mg/kg) and high doses (1.0-2.0 mg/kg) i.v. At 0.05 to 0.20 mg/kg sertindole (plasma concentrations 30-157 nM), QTc was prolonged by 1 to 5% in normal dogs and by 9 to 20% in dogs with remodeled hearts due to chronic atrioventricular block (CAVB). TdP was not induced at these doses in normal dogs or in CAVB dogs with reproducible induction of TdP by dofetilide in previous experiments. At 1.0 to 2.0 mg/kg sertindole (plasma concentrations 0.5-3.1 muM), QTc prolonged by 6 to 11% in normal dogs and by 22% in dofetilide-sensitive CAVB dogs. TdP occurred in three of five animals in the latter group. Thus, at high i.v. doses sertindole can pose a serious proarrhythmic risk when electrical remodeling of the ventricles is present. At clinically relevant doses, however, sertindole does not cause TdP in anesthetized dogs with normal or remodeled hearts.
Descriptors: behavior, cardiovascular system, transport and circulation, pharmacology, schizophrenia, behavioral and mental disorders, drug therapy, sudden cardiac death, heart disease, toxicity, drug induced, prevention and control, torsades de pointes arrhythmias, drug induced, prevention and control, electrophysiology, clinical techniques, i ca,l current, i ca,t current, i herg current, i kcnq1, kcne1 current, i kv4.3 current, i scn5a current, qt prolongation, chronic atrioventricular block.

Torp, R., E. Head, N.W. Milgram, F. Hahn, O.P. Ottersen, and C.W. Cotman (2000). Ultrastructural evidence of fibrillar beta-amyloid associated with neuronal membranes in behaviorally characterized aged dog brains. Neuroscience 96(3): 495-506. ISSN: 0306-4522.
Abstract: The aged dog brain accumulates beta-amyloid in the form of diffuse senile plaques, which provides a potentially useful in vivo model system for studying the events surrounding the deposition of beta-amyloid. We used postembedding immunocytochemistry at the electron microscopic level to determine the subcellular distribution of beta-amyloid 1-40 and beta-amyloid 1-42 peptides in the prefrontal and parietal cortex of behaviorally characterized dogs ranging in age from one to 17 years. Immunogold particles signaling beta-amyloid 1-42 occurred over intracellular and extracellular fibrils that were approximately 8 nm in width. Intracellular beta-amyloid 1-42 fibrils were found in close proximity to glial fibrillary acidic protein fibers within astrocytes, but only in cells with signs of plasma membrane disruption. Neuronal labeling of beta-amyloid 1-42 appears to be associated with the plasma membrane. Membrane-bound beta-amyloid 1-42 occurs in the form of fine fibrils that are embedded in the dendritic membrane and appear to project into the extracellular space as determined by quantitative analysis of the immunogold particle distribution. Bundles of beta-amyloid 1-42 were also closely associated and/or integrated with degenerating myelin sheaths of axons. In one dog that was impaired on several cognitive tasks, extensive beta-amyloid 1-42 deposition was associated with microvacuolar changes and vascular pathology. The present findings suggest that beta-amyloid 1-42 may be generated at the dendritic plasma membrane as well as in intracellular compartments. The close association between beta-amyloid 1-42 destroyed myelin suggests one possible new mechanism by which beta-amyloid 1-42 induces neurodegeneration.
Descriptors: nervous system, neural coordination, neurodegeneration, nervous system disease.

Traystman, R.J. (2003). Animal models of focal and global cerebral ischemia. ILAR Journal 44(2): 85-95. ISSN: 1084-2020.
NAL Call Number: QL55.A1I43
Abstract: The use of appropriate animal models is essential to predict the value and effect of therapeutic approaches in human subjects. Focal (stroke) and global (cardiac arrest) cerebral ischemia represents diseases that are common in the human population. Stroke and cardiac arrest, which are major causes of death and disability, affect millions of individuals around the world and are responsible for the leading health care costs of all diseases. Understanding the mechanisms of injury and neuroprotection in these diseases is critical if we are ever to learn new target sites to treat ischemia. There are many animal models available to investigate injury mechanisms and neuroprotective strategies. This review summarizes many (but not all) small and large animal models of focal and global cerebral ischemia and discusses their advantages and disadvantages.
Descriptors: animal models, stroke, focal, global, cerebral ischemia, injury, neuroprotection.

Varenika, V., P. Dickinson, J. Bringas, R. LeCouteur, R. Higgins, J. Park, M. Fiandaca, M. Berger, J. Sampson, and K. Bankiewicz (2008). Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery. Journal of Neurosurgery 109(5): 874-80. ISSN: 0022-3085.
Abstract: OBJECT: The authors have shown that convection-enhanced delivery (CED) of gadoteridol-loaded liposomes (GDLs) into different regions of normal monkey brain results in predictable, widespread distribution of this tracking agent as detected by real-time MR imaging. They also have found that this tracking technique allows monitoring of the distribution of similar nanosized agents such as therapeutic liposomes and viral vectors. A limitation of this procedure is the unexpected leakage of liposomes out of targeted parenchyma or malignancies into sulci and ventricles. The aim of the present study was to evaluate the efficacy of CED after the onset of these types of leakage. METHODS: The authors documented this phenomenon in a study of 5 nonhuman primates and 7 canines, comprising 54 CED infusion sessions. Approximately 20% of these infusions resulted in leakage into cerebral ventricles or sulci. All of the infusions and leakage events were monitored with real-time MR imaging. The authors created volume-distributed versus volume-infused graphs for each infusion session. These graphs revealed the rate of distribution of GDL over the course of each infusion and allowed the authors to evaluate the progress of CED before and after leakage. RESULTS: The distribution of therapeutics within the target structure ceased to increase or resulted in significant attenuation after the onset of leakage. CONCLUSIONS: An analysis of the cases in this study revealed that leakage undermines the efficacy of CED. These findings reiterate the importance of real-time MR imaging visualization during CED to ensure an accurate, robust distribution of therapeutic agents.
Descriptors: brain physiopathology, contrast media administration and dosage, convection, drug delivery systems methods, heterocyclic compounds administration and dosage, organometallic compounds administration and dosage, brain pathology, contrast media pharmacokinetics, dogs, heterocyclic compounds pharmacokinetics, liposomes pharmacokinetics, macaca fascicularis, magnetic resonance imaging, models, animal, organometallic compounds pharmacokinetics.

Wang, Q., Z. Wang, P. Zhu, and J. Jiang (2004). Alterations of myelin basic protein and ultrastructure in the limbic system at the early stage of trauma-related stress disorder in dogs. Journal of Trauma Injury Infection and Critical Care 56(3): 604-610. ISSN: 1079-6061.
Abstract: Background: The secondary injury and related complications after trauma are still the focus of trauma research. However, whether the remote effects on the central nervous system could be induced by high-energy missile extremity impact remains unclear. Also, the possible biomarker for brain damage in traumatic stress disorder has not been determined. Methods: Forty-two healthy adult dogs were divided into three groups: the control group (n = 12), the high-speed trauma group (n = 15), and the low-speed trauma group (n = 15). Bilateral thighs of dogs were wounded with a smoothbore 6.2-mm rifle at a speed of 1,368 m/s (1.03-g steel bullet) for the high-speed trauma group and 625 m/s for the low-speed trauma group. The expression of myelin basic protein (MBP) in cerebrospinal fluid (CSF), hypothalamus and hippocampus of the limbic system, and temporoparietal cortex was investigated by enzyme-linked immunosorbent assay and dot-blot analysis. Also, the ultrastructure of the above areas was observed with light and electron microscopy. Results: Neuronal degeneration and nerve fiber demyelination were seen in the hypothalamus and hippocampus in the high-speed trauma group at 8 hours after impact. The MBP level was markedly increased in the CSF (p < 0.01) in the two trauma groups, in the hypothalamus of the low-speed trauma group (p < 0.05), and in both the hypothalamus and the hippocampus of the high-speed trauma group (p 0.01). The expression of MBP mRNA was also significantly enhanced in these areas at the same time. The increase of MBP content in the CSF was positively correlated with the elevation of MBP concentration in the hypothalamus and hippocampus. Conclusion: The hypothalamus and hippocampus of the limbic system in the central nervous system are vulnerable to damage after high-energy missile extremity impact, indicating that it might be one of the important pathologic bases involved in the development of trauma-related complications. Meanwhile, the MBP level in the CSF may be a sensitive biological indicator for brain damage at the early stage of trauma-related stress disorder.
Descriptors: nervous system, neural coordination, brain damage, injury, neoplastic disease, diagnosis, trauma related stress disorder, injury, diagnosis, pathology, symptom, dot blot analysis, laboratory techniques, enzyme linked immunosorbent assay, immunologic techniques, laboratory techniques.

Yamato, O., Y. Masuoka, M. Yonemura, A. Hatakeyama, H. Satoh, A. Kobayashi, M. Nakayama, T. Asano, T. Shoda, M. Yamasaki, K. Ochiai, T. Umemura, and Y. Maede (2003). Clinical and clinico-pathologic characteristics of shiba dogs with a deficiency of lysosomal acid beta-galactosidase: a canine model of human gm1 gangliosidosis. Journal of Veterinary Medical Science 65(2): 213-217. ISSN: 0916-7250.
NAL Call Number: SF604.J342
Abstract: The present study was conducted to determine the clinical and clinico-pathologic characteristics of Shiba dogs with GM1 gangliosidosis, which is due to an autosomal recessively inherited deficiency of lysosomal acid beta-galactosidase activity. Clinical and clinico-pathological features were investigated in 10 homozygous Shiba dogs with GM1 gangliosidosis. The age at onset was 5 to 6 months and the dogs manifested progressive neurologic signs including loss of balance, intermittent lameness, ataxia, dysmetria and intention tremor of the head. The dogs were unable to stand by 10 months of age due to a progression of ataxia and spasticity in all limbs. Corneal clouding, a visual defect, generalized muscle rigospasticity, emotional disorder and a tendency to be lethargic were observed at 9 to 12 months. The dogs became lethargic from 13 months of age. The survival period seemed to be 14 to 15 months. As a clinico-pathologic feature, lymphocytes with abnormally large vacuoles were observed in peripheral blood (30 to 50% of total lymphocytes) through the lifetime of the dogs. The clinical and clinico-pathologic characteristics of this animal model are useful for not only the development and testing of potential methods of therapy, but also the diagnosis of affected homozygous Shiba dogs in veterinary clinics.
Descriptors: pathology, beta galactosidase, clinical aspects, disease models, dog breeds, enzyme activity, gangliosidosis, survival, metabolism, nervous system, neural coordination, veterinary medicine, medical sciences, GM1 gangliosidosis, genetic disease, metabolic disease, ataxia, nervous system disease, corneal clouding, eye disease, dysmetria, emotional disorder, behavioral and mental disorders, generalized muscle rigospasticity, tremor, balance loss, lameness, lethargy .

Yang, X.P. and S. Chiba (2003). Interaction between neuropeptide y y1 receptors and alpha1b-adrenoceptors in the neurovascular junction of canine splenic arteries. European Journal of Pharmacology 466(3): 311-315. ISSN: 0014-2999.
NAL Call Number: QP901.E8
Abstract: Previous study has demonstrated that periarterial electrical nerve stimulation (30-s trains of pulses at a frequency of 1 or 4 Hz) induces a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X-receptor-mediated constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated response in the isolated canine splenic artery. Treatment with 8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione (BMY 7378, 0.1 mumol/l), a selective alpha1D-adrenoceptor antagonist, produced a slight but significant inhibition of the second peaked responses. A marked inhibition of second peaked responses was obtained by exposure of the tissues to chloroethylclonidine (60 mumol/l), an alpha1B- and alpha1D-adrenoeptor antagonist. Neither BMY 7378 nor chloroethylclonidine affected the first peaked vasoconstrictor responses. (Leu31,Pro34)Neuropeptide Y (10-30 nmol/l), a selective neuropeptide Y Y1 receptor agonist, enhanced the second peaked responses in the presence of BMY 7378 but failed to enhance the responses in the presence of chloroethylclonidine. The results indicate that the postjunctional alpha1B-adrenoceptor subtype is likely coupled to neuropeptide Y Y1 receptors responsible for the cooperation of the sympathetic adrenergic and neuropeptide Yergic transmission in the canine splenic artery.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, pharmacology .

Yasukawa, T. (2002). Effects of inversed ratio ventilation (irv) on intracranial pressure (icp) in dogs with pulmonary edema. Kawasaki Igakkai Shi 28(4): 269-278. ISSN: 0386-5924.
Abstract: Although correlation between variations in the inspiratory to expiratory ratio (I:E ratio) and intracranial pressure (ICP) has not been clarified, the study of Mihira showed that IRV (at I:E ratios of 1.7:1, 2.3:1, and 4:1) does not influence ICP in dogs with normal or elevated ICP. In order to estimate the influence of lowered lung compliance on ICP during IRV, an additional study was designed to observe the effects of the I:E ratio=1:2 to 4:1 on ICP in 10 dogs with pulmonary edema induced by Oleic acid. Following baseline measurement of control ventilation (I:E ratio=1:2), lung edema was induced by venous injection of Oleic acid (0.05 mL/kg). After verifying the reduction of lung compliance, four different I:E ratios were applied in the order of I:E=1:2, 1.7:1, 2.3:1, and 4:1. Throughout the period of these measurements, PaCO2 constantly maintained normocapnia and arterial blood pressure was kept within normal range. Intracranial hemodynamics (ICP, cerebral perfusion pressure), lung mechanics (mean airway pressure (mAWP), peak inspiratory pressure (PIP), lung compliance), systemic hemodynamics (mean arterial pressure, mean pulmonary artery pressure, central venous pressure, cardiac output), and blood gases were measured at 30 min under every I:E ratio ventilatory mode. In these dogs with pulmonary edema, mAWP significantly increased during IRV in comparison with that during control ventilation (p<0.05), but there was no significant difference in PIP between control ventilation and IRV. ICP remained unchanged during IRV (12.5+-4.2, 10.0+-2.9, 11.1+-2.2, 11.3+-2.7 at I:E=1:2, 1.7:1, 2.3:1 and 4:1, respectively). This study suggested that IRV (at I:E ratios of 1.7:1, 2.3:1, and 4:1), which can minimize ventilator-induced lung injury, has no influence on ICP. Therefore, IRV may be one beneficial option as ventilation strategy for acute respiratory distress syndrome with intracranial hypertension.
Descriptors: methods and techniques, nervous system, neural coordination, respiratory system, respiration, acute respiratory distress syndrome, respiratory system disease, intracranial hypertension, nervous system disease, vascular disease, pulmonary edema, inversed ratio ventilation, laboratory techniques, intracranial pressure, mean airway pressure.
Language of Text: Japanese.

Yelmen, N.K., G. Sahin, T. Oruc, and M. Hacibekiroglu (2003). Hypoxic initiation of pulmonary hypertension is mediated by serotonin secretion from neuroepithelial bodies in chemodenervated dogs. Chinese Journal of Physiology 46(1): 27-33. ISSN: 0304-4920.
Abstract: The purpose of this study was to investigate the stimulatory effect of hypoxia on the secretion of serotonin by neuroepithelial bodies (NEB) as well as to determine the relation between its level and changes in pulmonary arterial pressure (PAP) and also to determinate the effect of serotonin antagonists (pizotifen and methysergide) on the responses of pulmonary and systemic arterial pressures. The experiments were carried out in peripheral chemoreceptor-denervated dogs anesthetized with Na penthabarbital (30 mg/kg i.v.). On the breathing of normoxic and hypoxic (7% O2-93% N2) gas mixtures and on the injection of KCN (80 mug/kg i.v.), PAP, systemic arterial blood pressure (BP), tidal volume (VT), respiratory frequency (f/min), ventilation minute volume (VE) were determined. Also PAP and BP were recorded before and after the injection of pizotifen (0.5 mg/kg i.v.) and methysergide (1 mg/kg i.v.) during normoxic or hypoxic gas mixture breathing. At the end of each experimantal phase, serotonin level, PaO2, PaCO2 and pHa values in blood samples obtained from left ventricle and femoral artery were determined. On the breathing of the hypoxic gas mixture of the chemodenervated dogs, VT, VE and BP significantly decreased (P<0.001, P<0.001, P<0.01). The mean value of PAP and serotonin levels (ventricular and femoral) were found significantly increased when compared with the corresponding normoxic values (P<0.001, P<0.05). On the other hand, injection of KCN produced no significant changes in PAP, serotonin levels, BP and respiratory parameters. After the injection of pizotifen, PAP was significantly increased in hypoxia (P<0.01). After the injection of methysergide, the response of PAP was completely abolished during the breathing of hypoxic gas mixture. The finding of the abolition of response of PAP to hypoxia after the injection of methysergide indicates that serotonin release from NEB may be responsible for the elevation of PAP in hypoxic hypoxia.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, respiratory system, respiration, veterinary medicine, medical sciences, hypoxia, respiratory system disease, pulmonary hypertension, chemodenervation, experimental surgical techniques, laboratory techniques, pulmonary arterial pressure [pap].

Zhong, H., B. Chen, S. Lu, M. Zhao, Y. Guo, and S. Hou (2007). Nerve regeneration and functional recovery after a sciatic nerve gap is repaired by an acellular nerve allograft made through chemical extraction in canines. Journal of Reconstructive Microsurgery 23(8): 479-87. ISSN: 0743-684X.
Abstract: The purpose of the present study is to test whether chemically extracted acellular nerve segments can be used to repair the sciatic nerve gap. Fifteen canines were divided into acellular nerve allografting group (ANG, six canines), autografting group (AG, six canines), and fresh nerve allografting group (FNG, three canines). The sciatic nerves on the right side of the animals were exposed, and 5-cm-long segments of the nerves were removed from the midthigh level and replaced by the three types of grafts. At 6 months after grafting, all animals in the ANG and AG had similar patterns of right posterior limb gait cycle and right ankle movements. Moreover, the animals in the ANG and AG had similar nerve regeneration, with dense regeneration fibers in the distal tibial nerves and obvious motor end plates in the target muscle. But in FNG, the area surrounding the graft was scarred as the result of inflammation, and there was a brown central area where there was little nerve regeneration. All of the above shows that chemical acellular nerve allografting can be used to repair a gap as long as 5 cm in the continuity of the sciatic nerve in canines and has similar effects to autografting.
Descriptors: nerve regeneration physiology, sciatic nerve physiology, axons ultrastructure, basement membrane transplantation, deoxycholic acid, detergents, dogs, electrophysiology, evoked potentials, motor, evoked potentials, somatosensory, gait, models, animal, nerve fibers, neural conduction, octoxynol, recovery of function, sciatic nerve injuries, sciatic nerve surgery, transplantation, autologous, transplantation, homologous.

Zhou, C., M. Yamaguchi, G. Kusaka, C. Schonholz, A. Nanda, and J.H. Zhang (2004). Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism 24(4): 419-431. ISSN: 0271-678X.
Abstract: Apoptosis in the endothelium of major cerebral arteries may play a role in the initiation and maintenance of cerebral vasospasm after subarachnoid hemorrhage (SAH). We tested the therapeutic effect of caspase inhibitors on endothelial apoptosis and on cerebral vasospasm in an established dog double-hemorrhage model. Thirty-one mongrel dogs were divided into five groups: control; SAH; SAH treated with vehicle (DMSO); SAH treated with Ac-DEVD-CHO (a specific caspase-3 inhibitor) and SAH treated with Z-VAD-FMK (a broad caspase inhibitor). The inhibitors (100 muM) were injected into the cisterna magna daily front Day 0 through Day 3. Angiography was performed on Day 0 and Day 7. Histology, TUNEL staining, and immunohistochemistry were conducted on basilar arteries collected on Day 7 after SAH. Positive staining of TUNEL, poly(ADP)-ribose polymerase (PARP), caspase-3, and caspase-8 was observed in the endothelial cells of the spastic arteries. Double fluorescence labeling demonstrated colocalization of TUNEL with caspase-3 and TNFalpha-receptor-1 (TNFR I). Ac-DEVD-CHO and Z-VAD-FMK prevented endothelial apoptosis and reduced angiographic vasospasm. The mechanism of apoptosis in endothelial cells involves TNFR1 and the caspase-8 and caspase-3 pathways. Caspase inhibitors may have potential in the treatment of cerebral vasospasm..
Descriptors: biochemistry and molecular biophysics, subarachnoid hemorrhage, nervous system disease, vascular disease, tunel, genetic techniques, laboratory techniques, cerebral vasospasm, endothelial apoptosis.

Zuperku, E.J., I.F. Brandes, A.G. Stucke, A. Sanchez, F.A. Hopp, and E.A. Stuth (2008). Major components of endogenous neurotransmission underlying the discharge activity of hypoglossal motoneurons in vivo. Advances in Experimental Medicine and Biology 605: 279-84. ISSN: 0065-2598.
NAL Call Number: QP901 .A33
Abstract: Multibarrel micropipettes were used to simultaneously record unit activity and apply antagonists on individual inspiratory hypoglossal motoneurons (IHMNs) to determine the endogenous activation levels of NMDA, non-NMDA, GABA(A) and serotonin receptors responsible for the IHMN spontaneous discharge patterns in decerebrate dogs. IHMN activity is highly dependent on glutamatergic phasic and tonic drives, which are differentially mediated by the receptor subtypes. Endogenous serotonin significantly amplifies IHMN activity, while GABAergic gain modulation acts to attenuate activity. Thus, alterations in the neurotransmission of any of these systems could markedly alter neuronal output to target muscles.
Descriptors: hypoglossal nerve physiology, motor neurons physiology, synaptic transmission physiology, 2 amino 5 phosphonovalerate pharmacology, bicuculline pharmacology, decerebrate state, dogs, excitatory amino acid antagonists pharmacology, ketanserin pharmacology, models, animal, models, neurological, quinoxalines pharmacology, tongue innervation.

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