International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats.

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals.The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures.Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements.The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations.

Clinical features, diagnosis, and survival analysis of dogs with glioma.

BACKGROUND: Gliomas in dogs remain poorly understood. OBJECTIVES: To characterize the clinicopathologic findings, diagnostic imaging features and survival of a large sample of dogs with glioma using the Comparative Brain Tumor Consortium diagnostic classification. ANIMALS: Ninety-one dogs with histopathological diagnosis of glioma. METHODS: Multicentric retrospective case series. Signalment, clinicopathologic findings, diagnostic imaging characteristics, treatment, and outcome were used. Tumors were reclassified according to the new canine glioma diagnostic scheme. RESULTS: No associations were found between clinicopathologic findings or survival and tumor type or grade. However, definitive treatments provided significantly (P = .03) improved median survival time (84 days; 95% confidence interval [CI], 45-190) compared to palliative treatment (26 days; 95% CI, 11-54). On magnetic resonance imaging (MRI), oligodendrogliomas were associated with smooth margins and T1-weighted hypointensity compared to astrocytomas (odds ratio [OR], 42.5; 95% CI, 2.42-744.97; P = .04; OR, 45.5; 95% CI, 5.78-333.33; P < .001, respectively) and undefined gliomas (OR, 84; 95% CI, 3.43-999.99; P = .02; OR, 32.3; 95% CI, 2.51-500.00; P = .008, respectively) and were more commonly in contact with the ventricles than astrocytomas (OR, 7.47; 95% CI, 1.03-53.95; P = .049). Tumor spread to neighboring brain structures was associated with high-grade glioma (OR, 6.02; 95% CI, 1.06-34.48; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with gliomas have poor outcomes, but risk factors identified in survival analysis inform prognosis and the newly identified MRI characteristics could refine diagnosis of tumor type and grade.

Expression of FOXP3 in Canine Gliomas: Immunohistochemical Study of Tumor-Infiltrating Regulatory Lymphocytes.

Dogs develop gliomas with similar histopathological features to human gliomas and share with them the limited success of current therapeutic regimens such as surgery and radiation. The tumor microenvironment in gliomas is influenced by immune cell infiltrates. The present study aims to immunohistochemically characterize the tumor-infiltrating lymphocyte (TIL) population of naturally occurring canine gliomas, focusing on the expression of Forkhead box P3-positive (FOXP3+) regulatory T-cells (Tregs). Forty-three canine gliomas were evaluated immunohistochemically for the presence of CD3+, FOXP3+, and CD20+ TILs. In low-grade gliomas, CD3+ TILs were found exclusively within the tumor tissue. In high-grade gliomas, they were present in significantly higher numbers throughout the tumor and in the brain-tumor junction. CD20+ TILs were rarely found in comparison to CD3+ TILs. FOXP3+ TILs shared a similar distribution with CD3+ TILs. The accumulation of FOXP3+ Tregs within the tumor was more pronounced in astrocytic gliomas than in tumors of oligodendroglial lineage and the difference in expression was significant when comparing low-grade oligodendrogliomas and high-grade astrocytomas. Only high-grade astrocytomas presented FOXP3+ cells with tumoral morphology. In spontaneous canine gliomas, TILs display similar characteristics (density and distribution) as described for human gliomas, supporting the use of the dog as an animal model for translational immunotherapeutic studies.

Characterization of the canine rostral ventricular-subventricular zone: Morphological, immunohistochemical, ultrastructural, and neurosphere assay studies.

The mammalian ventricular-subventricular zone (V-SVZ) presents the highest neurogenic potential in the brain of the adult individual. In rodents, it is mainly composed of chains of neuroblasts. In humans, it is organized in layers where neuroblasts do not form chains. The aim of this study is to describe the cytoarchitecture of canine V-SVZ (cV-SVZ), to assess its neurogenic potential, and to compare our results with those previously described in other species. We have studied by histology, immunohistochemistry (IHC), electron microscopy and neurosphere assay the morphology, cytoarchitecture and neurogenic potential of cV-SVZ. Age groups of animals were performed. Histological and ultrastructural studies indicated that the cV-SVZ is organized in layers as in humans, but including migratory chains as in rodents. Neural progenitors were organized in niches in the subependymal area and a decline in their number was observed with age. Adult-young dogs contained migratory cells capable to expand and differentiate in vitro according with previous results obtained in rodents, primates, humans, pigs, and dogs. Some adult animals presented perivascular niches outside the V-SVZ. Our observations evidence a great similarity between canine and human V-SVZ indicating that the dog may be better representative of neurogenic events in humans, compared with rodents. Accordingly with our results, we conclude that dogs are a valuable animal model of adult neurogenesis in comparative and preclinical studies.