Restricted Sensitivity of FJ-C Staining to Assess Neuronal Degeneration and Death in Preclinical Mouse Studies.

Fluorescein-derived fluorochromes and anionic dyes such as Fluoro-Jade (FJ) stains have been introduced to facilitate recognition of dying neurons in tissue sections. However, the definition of what is really detected by FJ-based stains and its sensitivity in the detection of neuronal cell death is unclear. In our work, we evaluated the outcome of FJ-C staining in mouse brains from 4 different well-characterized models of neurodegeneration. Neuronal degeneration and loss were highlighted with high sensitivity by FJ-C stain in mice with dysfunctional γ-secretase in the glutamatergic neurons and in mice affected by acute cerebral ischemia. Histopathologically, acute eosinophilic necrosis or "red dead" neurons were associated with FJ-C staining in both settings. Conversely, in mice affected by chronic cerebral microinfarcts due to tumor lysis syndrome as well as in a model of mitochondrial encephalopathy, FJ-C staining failed to detect neuronal death. Histopathologically, these models were characterized by extensive neuronal vacuolation associated with fading neurons ("ghost cells"). Therefore, contrary to the widespread belief that FJ-C stain has high affinity for all degenerating neurons regardless of the underlying cell death mechanism, we observed restricted sensitivity of the technique to specific conditions of neuronal cell death. As such, complementary techniques are essential to evaluate the presence of neurodegeneration in the absence of a positive FJ-C signal.

Heavy metals obtained from waterways induced neurodegeneration in the prefrontal cortex of Wistar rats

The level of heavy metals in Nigeria waterways is grossly influenced by the irrepressible disposal and recycling of electronic waste. The impact of heavy metals obtained from waterways on the prefrontal cortex of experimental rats was investigated in this study. Thirty (30) adult male Wistar rats weighing about 150-180 g were used in this study. Ten rats apiece were assigned randomly into three groups. Pooled sampled water and water containing the highest average concentration of combined heavy metals recorded in the waterways was given to the Wistar rats within the treatment groups ad libitum for 65 days. Blood sera were obtained for analysis of oxidative stress markers. The prefrontal cortex was processed for paraffin embedding, and sections stained for histological, histochemical and immunochemical evaluations. P < 0.05 was regarded as significant for data using one-way analysis of variance. Oxidative damage was observed in animals from the treatment groups when compared to the control. The analysed levels of oxidative stress markers showed statistically significant differences, except between groups given pooled sampled water and combined metals. Neurodegeneration was attested from the histological and histochemical evaluations, and the immunohistochemical evaluation revealed marked astrocytosis with induced oxidative stress while comparing the experimental groups

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Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin α5ß1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement To Promote Its Invasion of N2a Cells.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic virus that causes diffuse neuronal infection with neurological damage and high mortality. Virus-induced cytoskeletal dynamics are thought to be closely related to this type of nerve damage. Currently, the regulation pattern of the actin cytoskeleton and its molecular mechanism remain unclear when PHEV enters the host cells. Here, we demonstrate that entry of PHEV into N2a cells induces a biphasic remodeling of the actin cytoskeleton and a dynamic change in cofilin activity. Viral entry is affected by the disruption of actin kinetics or alteration of cofilin activity. PHEV binds to integrin α5ß1 and then initiates the integrin α5ß1-FAK signaling pathway, leading to virus-induced early cofilin phosphorylation and F-actin polymerization. Additionally, Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division cycle 42 (Cdc42), and downstream regulatory gene p21-activated protein kinases (PAKs) are recruited as downstream mediators of PHEV-induced dynamic changes of the cofilin activity pathway. In conclusion, we demonstrate that PHEV utilizes the integrin α5ß1-FAK-Rac1/Cdc42-PAK-LIMK-cofilin pathway to cause an actin cytoskeletal rearrangement to promote its own invasion, providing theoretical support for the development of PHEV pathogenic mechanisms and new antiviral targets.IMPORTANCE PHEV, a member of the Coronaviridae family, is a typical neurotropic virus that primarily affects the nervous system of piglets to produce typical neurological symptoms. However, the mechanism of nerve damage caused by the virus has not been fully elucidated. Actin is an important component of the cytoskeleton of eukaryotic cells and serves as the first obstacle to the entry of pathogens into host cells. Additionally, the morphological structure and function of nerve cells depend on the dynamic regulation of the actin skeleton. Therefore, exploring the mechanism of neuronal injury induced by PHEV from the perspective of the actin cytoskeleton not only helps elucidate the pathogenesis of PHEV but also provides a theoretical basis for the search for new antiviral targets. This is the first report to define a mechanistic link between alterations in signaling from cytoskeleton pathways and the mechanism of PHEV invading nerve cells.

Abnormal locomotor muscle recruitment activity is present in horses with shivering and Purkinje cell distal axonopathy.

BACKGROUND: Cerebellar Purkinje cell axonal degeneration has been identified in horses with shivering but its relationship with abnormal hindlimb movement has not been elucidated. OBJECTIVES: To characterise surface electromyographic (sEMG) hindlimb muscle activity in horses with shivering, correlate with clinical scores and examine horses for Purkinje axonal degeneration. STUDY DESIGN: Descriptive controlled clinical study. METHODS: The hindlimb of seven shivering and six control draught horses were clinically scored. Biceps femoris (BF), vastus lateralis (VL), tensor fasciae latae and extensor digitorum longus were recorded via sEMG during forward/backward walking and trotting. Integrated (iEMG) and peak EMG activity were compared between groups and correlated with clinical locomotor exam scores. Sections of the deep cerebellar nuclei (DCN) of six of the seven shivering horses were examined with calbindin immunohistochemistry. RESULTS: In control horses, backward walking resembled forward walking (right hindlimb peak EMG: backward: 47.5 ± 21.9%, forward: 36.9 ± 15.7%) but displayed significantly higher amplitudes during trotting (76.1 ± 3.4%). However, in shivering horses, backward walking was significantly different from forward (backward: 88.5 ± 21.5%, forward: 49.2 ± 8.9%), and resembled activity during trotting (81.4 ± 4.8%). Specific to backward walking, mean sEMG amplitude fell outside two standard deviations of mean control sEMG for ≥25% of the stride in the BF for all seven and the VL for six of the seven shivering horses. Locomotor exam scores were correlated with peak EMG (r = 0.87) and iEMG (r = 0.87). Calbindin-positive spheroids were present in Purkinje axons in DCN of all shivering horses examined. MAIN LIMITATIONS: The neuropathological examination focused specifically on the DCN and, therefore, we cannot fully exclude additional lesions that may have influenced abnormal sEMG findings in shivering horses. CONCLUSION: Shivering is characterised by abnormally elevated muscle recruitment particularly in BF and VL muscles during backward walking and associated with selective Purkinje cell distal axonal degeneration.

Abiotrofia cerebelar em um gato: relato de caso / Cerebellar abiotrophy in a feline: case report

Um caso de abiotrofia cerebelar em um gato com 45 dias de idade foi diagnosticado no Laboratório de Patologia Animal, Hospital Veterinário da Universidade Federal de Campina Grande. O animal apresentava, havia 15 dias, apatia, anorexia, desidratação, ataxia, hipermetria, espasticidade dos membros torácicos e pélvicos, tremores de intenção, nistagmo, opistótono, déficit proprioceptivo e ausência de resposta de ameaça. Clinicamente, havia a suspeita de hipoplasia cerebelar, e, devido ao prognóstico desfavorável, o animal foi eutanasiado. Na necropsia, não foram observadas alterações macroscópicas. Microscopicamente, as lesões estavam restritas ao cerebelo e caracterizavam-se por alterações neurodegenerativas e necróticas, com desaparecimento segmentar dos neurônios de Purkinje. Nessas áreas, também se verificaram espaços em branco, denominado aspecto de cesto vazio, resultantes da perda dos neurônios de Purkinje, além de raros esferoides axonais e proliferação dos astrócitos de Bergmann. Em algumas áreas, a camada granular estava hipocelular e havia moderada gliose multifocal na camada molecular. O diagnóstico de abiotrofia cerebelar foi realizado com base nos dados epidemiológicos, clínicos e, principalmente, pelas alterações histopatológicas dos neurônios de Purkinje características da doença.(AU)

The aim of this report was to describe a case of cerebellar abiotrophy in cat with 45-year-old diagnosed at the Animal Pathology Laboratory, Veterinary Hospital of the Federal University of Campina Grande. The animal had presented 15-day apathy, anorexia, dehydration and neurological signs, characterized by ataxia, hypermetria, spasticity of fore and hindlimbs, intention tremor, nystagmus, opisthotonos, proprioceptive deficits, and absence of threat response. Clinically, cerebellar hypoplasia was suspected and the animal was euthanized due to poor prognosis. During necropsy, gross lesions were not observed. Microscopically the lesions were restricted to the cerebellum and were characterized by neurodegenerative and necrotic damage with segmental disappearance of the Purkinje cells. In these areas, there were also empty spaces, called the empty basket aspect, resulting from the loss of Purkinje cells, as well as rare axonal spheroids and proliferation of Bergmann's astrocytes. In some areas, the granular layer was hypocellular and there was moderate multifocal gliosis in the molecular layer. The diagnosis of cerebellar abiotrophy was based on epidemiological, clinical and mainly on histopathological changes in neurons of Purkinje disease characteristics.(AU)

A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2).

Spongy degeneration with cerebellar ataxia (SDCA) is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified an ∼10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole-genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the ß2 subunit of the Na+/K+-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276). The SINE insertion caused aberrant RNA splicing. Immunohistochemistry suggested a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knockout mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2). Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2-affected Malinois puppies may serve as a naturally occurring animal model for this disorder.

The Equine Movement Disorder "Shivers" Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration.

"Shivers" is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the pathologic mechanisms of the disease is known, nor has a neuroanatomic locus been identified, we undertook a detailed neuroanatomic and neuropathologic analysis of the complete sensorimotor system in horses with shivers and clinically normal control horses. No abnormalities were identified in the examined hind limb and forelimb skeletal muscles nor the associated peripheral nerves. Eosinophilic segmented axonal spheroids were a common lesion. Calretinin-positive axonal spheroids were present in many regions of the central nervous system, particularly the nucleus cuneatus lateralis; however, their numbers did not differ significantly from those of control horses. When compared to controls, calretinin-negative, calbindin-positive, and glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers. Unusual lamellar or membranous structures resembling marked myelin decompaction were present between myelin sheaths of presumed Purkinje cell axons in the deep cerebellar nuclei of shivers but not control horses. The immunohistochemical and ultrastructural characteristics of the lesions combined with their functional neuroanatomic distribution indicate, for the first time, that shivers is characterized by end-terminal neuroaxonal degeneration in the deep cerebellar nuclei, which results in context-specific hypermetria and myoclonus.

Key-Gaskell syndrome in Brazil: first case report / Síndrome de Key-Gaskell: primeiro relato de caso no Brasil

Feline dysautonomia is a devastating disease characterized by neuronal degeneration in autonomic ganglia that results in clinical signs related to dysfunction of the sympathetic and parasympathetic nervous systems. The cause is unknown and this disease has a poor prognosis and no definitive treatment. Most reports have been described in few countries around the world, but the prevalence may be underestimated in countries like Brazil. This study describes the progression and clinicopathological changes of dysautonomia in a 17-month-old female Brazilian shorthair cat...

Disautonomia felina é uma doença devastadora, caracterizada por degeneração neuronal em gânglios autonômicos, a qual resulta em sinais clínicos relacionados à disfunção dos sistemas simpático e parassimpático. Sua causa é desconhecida, o prognóstico desfavorável e não há tratamento definitivo disponível. A maioria dos relatos foi descrita em países ao redor do mundo, mas sua prevalência pode estar subestimada em países como o Brasil. Este estudo descreve a progressão e as alterações clínico-patológicas da disautonomia em um gato de pelo curto brasileiro, do sexo feminino, de 17 meses de idade...

Neuronal loss and decreased GLT-1 expression observed in the spinal cord of Pembroke Welsh Corgi dogs with canine degenerative myelopathy.

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease that is frequently found in Pembroke Welsh Corgi (PWC) dogs. Canine DM is potentially a spontaneous animal model for human amyotrophic lateral sclerosis (ALS) because of similar lesions and the involvement of superoxide dismutase 1 (SOD1) mutation. However, the ventral horn lesion in DM has not been characterized in detail. Glutamate excitotoxicity due to deficiency of the glutamine-glutamate cycle has been implicated in neuron death in ALS. Thus, we examined 5 PWC dogs with an SOD1 mutation that were affected by DM, 5 non-DM PWC dogs, and 5 Beagle dogs without neurologic signs to assess the neuronal changes and the expression levels of 2 glial excitatory amino acid transporters (glutamate transporter 1 [GLT-1] and glutamate/aspartate transporter [GLAST]). The number of neurons in the spinal ventral horns of the DM dogs was significantly decreased, whereas no change was found in the cell size. Chromatolysis, lipofuscin-laden neurons, and marked synapse loss were also observed. GLT-1 expression was strikingly decreased in DM dogs, whereas GLAST expression showed no significant change. The results indicate that excitotoxicity related to the reduced expression of GLT-1, but not GLAST, may be involved in neuron loss in DM, as in human ALS, whereas intraneuronal events may differ between the 2 diseases.

Sexual metabolic differences in the rat limbic brain / Diferencias metabólicas sexuales en el cerebro límbico de rata

Background: There is actually limited evidence about the influence of estrogens on neuronal energy metabolism or functional cerebral asymmetry. In order to evaluate this relationship, eight male and sixteen female adult Wistar rats, divided into estrus and diestrus phase, were used to measure basal neuronal metabolic activity in some of the structures involved in the Papez circuit, using cytochrome c oxidase (C.O.) histochemistry. Method: We used C.O. histochemistry because cytochrome oxidase activity can be considered as a reliable endogenous marker of neuronal activity. Results: We found higher C.O. activity levels in diestrus as compared to estrus and male groups in the prefrontal cortex and thalamus. Conversely, neuronal oxidative metabolism was significantly higher in estrus than in diestrus and male groups in the dorsal and ventral hippocampus (CA1 and CA3) and in the mammillary bodies. However, no hemispheric functional lateralization was found in estrus, diestrus or male groups by C.O. activity. Conclusions: These results suggest a modulatory effect of estrogens on neuronal oxidative metabolism (AU)

Antecedentes: existe poca evidencia acerca de la influencia de los estrógenos sobre el metabolismo energético cerebral o la asimetría cerebral funcional. Para evaluarlo, se utilizaron ocho machos y dieciséis hembras de rata adultas de la cepa Wistar, divididas en fase estro y diestro, con el fin de medir la actividad metabólica neuronal basal en algunas de las estructuras cerebrales del circuito de Papez. Método: utilizamos la histoquímica de la citocromo c oxidasa (C.O.) porque su actividad puede ser considerada como un relevante marcador endógeno de la actividad neuronal. Resultados: encontramos mayores niveles de C.O. en el diestro en comparación con el estro y los machos en la corteza prefrontal y el tálamo. El metabolismo oxidativo neuronal fue significativamente mayor en el estro en comparación con el grupo diestro y los machos en el hipocampo dorsal y ventral (CA1 y CA3), así como en los cuerpos mamilares. No se encontró ninguna lateralización hemisférica funcional en los grupos experimentales. Conclusiones: estos resultados sugieren un efecto modulador de los estrógenos sobre el metabolismo oxidativo neuronal (AU)

Alterações no SNC e morfometria cerebelar de bovinos intoxicados experimentalmente por Solanum paniculatum / Alterations in the CNS and cerebellar morphometry of cattle experimentally poisoned by Solanum paniculatum

Algumas espécies de Solanum causam intoxicações em ruminantes caracterizadas clinicamente por desordens cerebelares e microscopicamente como doença do depósito lisossomal. Não há lesões de necropsia específicas e microscopicamente ocorrem vacuolização e perda de neurônios de Purkinje. Por ser Solanum paniculatum a espécie de ocorrência na região Nordeste, sendo responsável pelos surtos de intoxicação espontânea descrito no Estado de Pernambuco foi realizado um delineamento experimental para caracterizar o quadro clínico-patológico da intoxicação. Foram usados cinco bovinos, sendo quatro no grupo experimental (GE) e um animal no controle (GC), de seis meses de idade, sem raça definida, com peso de 120 Kg, mantidos em baias durante cinco meses na Clínica de Bovinos de Garanhuns/UFRPE. Os animais receberam a planta, colhida nas propriedades em que ocorreram os surtos naturais, na dosagem de 5g/kg/PV/dia da planta dessecada misturada na ração por ingestão natural. Semanalmente realizou-se o Head Raising Test para determinar os sinais cerebelares e quando positivo os animais foram submetidos à colheita de sangue e do líquido céfalo-raquidiano e em seguida foi feito à eutanásia.

O SNC e a rete mirabile foram fixados em formol a 10% tamponado, processados rotineiramente e corados pela hematoxilina e eosina para avaliação histopatológica. Foi realizada análise morfométrica das lesões cerebelares. Para avaliação dos resultados laboratoriais utilizou-se análise descritiva e em relação à morfometria, empregou-se o teste T de Student (p<0.05) na contagem de células de Purkinje e para a espessura da camada molecular do cerebelo o teste de Mann Whitney, com nível de 5% de significância. Três animais apresentaram sinais de intoxicação com tempo em média de 90 dias e um com 155 dias. Os sinais clínicos observados foram ataques convulsivos transitórios, e distúrbios do equilíbrio. Na necropsia não foram encontradas lesões específicas da intoxicação. Não houve alterações no hemograma e no líquido céfalo-raquidiano causado pela planta. No histopatológico havia principalmente vacuolização fina do pericário e perda de células de Purkinje, com degeneração Walleriana e esferóides axonais na camada granular e na substância branca medular, com proliferação dos astrócitos de Bergman. Vacuolização e necrose neuronal também foram observadas no óbex, pedúnculos cerebelares e colículos rostral e caudal e raramente no tálamo, núcleos da base, hipocampo e medula oblonga. Na análise morfométrica não houve diferença significativa (p<0,05) entre o número de células de Purkinje e a espessura da camada molecular entre o GE e GC, demonstrando que apesar dos bovinos desenvolverem quadro clínico da intoxicação e alterações histopatológicas acentuadas, mas nestas condições experimentais não ocorreram alteração morfométricas significativas em relação ao GC.

Sugerindo que há necessidade de um tempo de administração maior da planta para o aparecimento de lesões mais acentuadas como as que ocorrem em casos naturais. Os resultados laboratoriais de sangue e do líquido céfalo-raquidiano não refletem alterações relacionadas à intoxicação pela planta.

Some species of Solanum cause poisoning in ruminants clinically characterized by cerebellar disorders and microscopically lysosomal storage disease. There are no specific necropsy injuries and microscopically occurs vacuolation and Purkinje cells loss. Since Solanum paniculatum is the species of greater occurrence in the Northeast region of Brazil and is responsible for spontaneous intoxication outbreaks in Pernambuco State, an experimental delineation was carried out to characterize the clinical and pathological condition of the intoxication. Five cattle were randomly allotted in two groups, with four animals in the experimental group (EG) and one animal as control (CG), with six months of age, no defined breed and weighting 120 kg. All animals were kept in stalls along 5 months in the Clínica de Bovinos de Garanhuns/UFRPE. All animals from the experimental group were fed 5g/kg/body weight/day of the dried leaves of S. paniculatum which was mixed in the ration. The plant was collected in farms where outbreaks of intoxication were described. A Head Raising Test was weekly performed to determine the occurrence of any cerebellum clinical signs and when the result was positive the animal was submitted to a blood and cerebrospinal fluid sampling and subsequently euthanized.

Partial brachial plexus paresis in three calves.

Partial brachial plexus paresis was diagnosed in three calves with unilateral functional lameness in a forelimb based on clinical and neurologic examinations. Clinical signs of radial nerve paresis were the main presenting problems. Electromyography was used to identify the affected nerves with the calves under general anaesthesia. Abnormal spontaneous activity of denervated muscles showed that the radial, musculocutaneous, median and ulnar nerves were compromised. The calves were treated medically, using splint bandages, and with physiotherapy. All calves regained function of the affected legs and normal weight bearing.

Acute respiratory distress in an alpaca.

An alpaca was presented with a history of respiratory difficulty and death. Histology of the phrenic nerves and diaphragm revealed degenerative changes consistent with denervation atrophy, and a diagnosis of diaphragmatic paralysis was established. No gross or histological abnormalities were observed in the spinal cord or other organs. The etiology of the phrenic nerve neuropathy could not be determined. The need to examine phrenic nerves and diaphragm in camelids with respiratory distress is emphasized, as failure to examine these samples will preclude a diagnosis of diaphragmatic paralysis.

Increased immunohistochemical labelling for prion protein occurs in diverse neurological disorders of sheep: relevance for normal cellular PrP function.

The classical prion diseases (e.g. scrapie of sheep and goats and bovine spongiform encephalopathy of cattle) are characterized by the accumulation of abnormal forms of the prion protein (PrP), usually recognized by their relative resistance to proteolysis compared with the physiological cellular forms of PrP. However, novel prion diseases have been detected in sheep, cattle and man, in which the abnormal PrP has less resistance to proteolysis than identified previously. These more subtle differences between abnormal and normal forms of PrP can be problematic in routine diagnostic tests and raise questions in respect of the range of PrP disorders. Abnormal accumulations of PrP in atypical and classical prion diseases can be recognized by immunohistochemistry. To determine whether altered PrP expression or trafficking might occur in nosological entities not previously connected with prion disease, the brains of sheep affected with diverse neurological conditions were examined for evidence of altered PrP labelling. Such altered immunolabelling was detected in association with either basic lesions or specific diseases. Some reactive glial cells and degenerate neurons found in several different recognized disorders and non-specific inflammatory processes were associated with abnormal PrP labelling, which was absent from brains of healthy, age-matched sheep. The results agree with previous indications that normal PrP function may be linked with the oxidative stress response, but the data also suggest that PrP functions are more extensive than simple protective responses against stress insults.

Electrophysiologic evidence of polyneuropathy in a cat with signs of bilateral brachial plexus neuropathy.

CASE DESCRIPTION: A 2-year-old spayed female domestic shorthair cat was examined because of bilateral thoracic limb weakness of acute onset. CLINICAL FINDINGS: Clinical signs included muscle atrophy, paresis, depressed spinal reflexes, hyperesthesia of the thoracic limbs, and reduced jaw muscle tone. Pelvic limb reflexes were normal. Results of a neurologic examination were suggestive of multifocal lesions involving both brachial plexuses and the trigeminal nerves. Abnormal nerve conduction across the brachial plexus and delayed late potentials were found on electrodiagnostic testing, and diffuse subclinical involvement of other regions of the peripheral nervous system was confirmed on the basis of abnormal electromyographic findings for the masticatory muscles and conduction block of the peroneal nerve. TREATMENT AND OUTCOME: No specific treatments were given, and neurologic signs resolved within a month. A relapse occurred 2 months after the first episode, with clinical signs affecting both the pelvic and the thoracic limbs on this occasion. Again, the condition resolved without specific treatment, and 13 months after the initial episode, the cat reportedly was normal. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that brachial plexus neuropathy can be a multifocal disease in cats, even if clinically apparent neurologic deficits are initially subtle or absent, and that electrodiagnostic techniques can be used to identify subclinical involvement of the peripheral nerves.

Are ovine fenugreek (Trigonella foenum-graecum) staggers and kangaroo gait of lactating ewes two clinically and pathologically similar nervous disorders?

Fenugreek staggers has occurred in sheep in Victoria, as both an acute and a chronic syndrome. Signs included quadraparesis, a high stepping fore limb gait and a 'bunny-hopping' hind limb gait. Changes consistent with acute oedema were found in the brain and spinal cord of acute cases, and Wallerian degeneration in the peripheral nerves of chronic cases. Kangaroo gait occurred in ewes in New South Wales, and the clinical signs and microscopic changes were remarkably similar to those of fenugreek staggers. Although the diet associated with each is different the causal agent may be the same.

Beta-amyloid cortical deposits are accompanied by the loss of serotonergic neurons in the dog.

Dogs may naturally suffer an age-related cognitive impairment that has aroused a great deal of interest, even beyond the field of the veterinary clinic. This canine senile dementia reproduces several key aspects of Alzheimer's disease (AD), including the presence of beta-amyloid (A beta) deposits in the cerebral cortex, neurodegeneration, and learning and memory impairments. In the present study, we have used unbiased stereological procedures to estimate the number of the dorsal and median raphe nuclei (DRN and MRN, respectively) serotonergic neurons immunolabeled with an anti-tryptophan hydroxylase (TrH) monoclonal antibody in young and aged dogs without A beta cortical deposits and in aged dogs with A beta cortical deposits. The estimated total number of TrH-labeled neurons (mean +/- SD) was 94,790 +/- 26,341 for the DRN and 40,404 +/- 8,692 for the MRN. The statistical analyses revealed that aged dogs with A beta cortical pathology had 33% fewer serotonergic neurons in the DRN and MRN than aged dogs without A beta cortical deposits (108,043 +/- 18,800 vs. 162,242 +/- 39,942, respectively; P = 0.01). In contrast, no significant variations were found between young and aged dogs without A beta cortical deposits. These results suggest that degeneration of the serotonergic neurons could be involved in the cognitive damage that accompanies A beta cortical pathology in the dog and reinforce the use of the canine model for exploring the potential mechanisms linking the cortical A beta pathology and serotonergic neurodegeneration that occurs during the course of AD.

Neuropathologic findings in an aged albino gorilla.

Pallido-nigral spheroids associated with iron deposition have been observed in some aged clinically normal nonhuman primates. In humans, similar findings are observed in neurodegeneration with brain iron accumulation diseases, which, in some cases, show associated mutations in pantothenate kinase 2 gene (PANK2). Here we present an aged gorilla, 40 years old, suffering during the last 2 years of life from progressive tetraparesis, nystagmus, and dyskinesia of the arms, hands, and neck, with accompanying abnormal behavior. The postmortem neuropathologic examination revealed, in addition to aging-associated changes in the brain, numerous corpora amylacea in some brain areas, especially the substantia nigra, and large numbers of axonal spheroids associated with iron accumulation in the internal globus pallidus. Sequencing of the gorilla PANK2 gene failed to detect any mutation. The clinical, neuropathologic, and genetic findings in this gorilla point to an age-related pallido-nigral degeneration that presented PKAN-like neurologic deficits.