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• W3007567013 abstract "Epilepsy is the most common chronic neurological disease in dogs. The aim of treatment is seizure freedom but cannot be achieved in many cases. Successful treatment is considered a useful decrease in seizure frequency. To improve the outcome, a constant search for new treatment strategies is performed, influencing either the disease or epileptogenesis. Biomarkers are needed in neuroscience to depict changes on cellular or molecular level within the brain’s specific microenvironment. Finding useful biomarkers in epilepsy could support the search for new therapeutic strategies. In the current thesis, we have evaluated two potential prognostic biomarkers, glial fibrillary acidic protein (GFAP) and interleukin-1β (IL-1β) and one receptor possibly involved in pathogenesis of canine epilepsy, the cannabinoid receptor type-1 (CB1R). In the first part of the study GFAP, the main intermediate filament protein in astrocytes, was evaluated as potential biomarker for intracranial disorders using an ELISA. Healthy beagles and dogs with the clinical diagnoses idiopathic epilepsy, brain tumor, inflammation, spinal cord injury (SCI) and traumatic brain injury (TBI) were included. Significant differences were found between GFAP CSF levels of dogs with tumor and epilepsy and between inflammatory diseases and epilepsy. Furthermore, in TBI patients, high serum GFAP levels had a strong correlation with the Glasgow Coma Scale score. In dogs with SCI no significant difference between chronic and acute cases and severity of clinical signs could be detected. The second part of the project focused on the possible involvement of IL-1β, a potent proinflammatory cytokine, in neuroinflammation in epilepsy. Levels of IL-1β in serum and CSF were measured using an ELISA and compared between healthy dogs and TBI and epilepsy patients. IL-1β concentrations in CSF were not detectable. Additionally, serum values were not elevated in dogs with TBI in comparison to healthy controls. However, dogs with epilepsy had increased levels of IL-1β in serum regardless of the underlying cause of the disease. In the last part of the study, we investigated the expression of CB1R in hippocampus of epileptic dogs and quantitatively compared it to control animals. For that purpose, brain tissues of control dogs, dogs with idiopathic and structural epilepsy were CB1R immunolabeled using immunohistochemistry and double immunofluorescence staining. Expression of CB1R was qualitatively and quantitatively evaluated in several regions of hippocampus. Moreover, the number of CB1R positive astrocytes in dentate gyrus (DG) was compared between the groups of animals. In epileptic dogs a disease associated reorganization of CB1R expression was observed. In dogs with idiopathic epilepsy the CB1R expression was significantly decreased in the CA1 region compared to controls. Conversely, hippocampus of dogs with structural epilepsy revealed a significant increase in CB1R staining intensity in comparison to controls. Comparison of idiopathic and structural tissue demonstrated that both, the immunopositive area and the optical density of the staining reached significantly higher levels in patients with structural epilepsy. In addition, about 50% of astrocytes displayed positive CB1R staining in the tissue examined. In the current search for different biomarkers in canine epilepsy, the most important findings were that GFAP levels in CSF reflect severe structural changes in the brain parenchyma and GFAP serum levels in TBI may predict the outcome; IL-1β in serum is increased in epilepsy independent of the etiology of the seizures; CB1R expression in canine hippocampus was increased in structural epilepsy and downregulated in idiopathic epilepsy patients and more than 50% of astrocytes expressed CB1R. These findings, especially the disease associated influences need to be considered, when further validating new treatment approaches for dogs with epilepsy." @default.
• W3007567013 created "2020-03-06" @default.
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• W3007567013 date "2018-01-01" @default.
• W3007567013 modified "2023-09-24" @default.
• W3007567013 title "Search for biomarkers and pathogenesis studies in canine epilepsy" @default.
• W3007567013 hasPublicationYear "2018" @default.
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