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Detection of blood‐brain barrier dysfunction using advanced imaging methods to predict seizures in dogs with meningoencephalitis of unknown origin
Authors:Erez Hanael  Shelly Baruch  Orit Chai  Zohar Nir  Kira Rapoport  Marco Ruggeri  Itzhak Eizenberg  Dana Peery  Alon Friedman  Merav H Shamir
Institution:1. Hebrew University Koret School of Veterinary Medicine‐Veterinary Teaching Hospital, Rehovot Israel ; 2. Departments of Physiology and Cell Biology, Brain, and Cognitive Sciences, Zlotowski Center for Neuroscience, Ben‐Gurion University of the Negev, Beer Sheva Israel ; 3. Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax NS, Canada
Abstract:BackgroundThe blood‐brain barrier (BBB), which separates the intravascular and neuropil compartments, characterizes the vascular bed of the brain and is essential for its proper function. Recent advances in imaging techniques have driven the development of methods for quantitative assessment of BBB permeability.Hypothesis/ObjectivesPermeability of the BBB can be assessed quantitatively in dogs with meningoencephalitis of unknown origin (MUO) and its status is associated with the occurrence of seizures.AnimalsForty dogs with MUO and 12 dogs without MUO.MethodsRetrospective, prospective cohort study. Both dynamic contrast enhancement (DCE) and subtraction enhancement analysis (SEA) methods were used to evaluate of BBB permeability in affected (DCE, n = 8; SEA, n = 32) and control dogs (DCE, n = 6; SEA, n = 6). Association between BBB dysfunction (BBBD) score and clinical characteristics was examined. In brain regions where BBBD was identified by DCE or SEA magnetic resonance imaging (MRI) analysis, immunofluorescent staining for albumin, glial fibrillary acidic protein, ionized calcium binding adaptor molecule, and phosphorylated mothers against decapentaplegic homolog 2 were performed to detect albumin extravasation, reactive astrocytes, activated microglia, and transforming growth factor beta signaling, respectively.ResultsDogs with BBBD had significantly higher seizure prevalence (72% vs 19%; P = .01) when compared to MUO dogs with no BBBD. The addition of SEA to routine MRI evaluation increased the identification rate of brain pathology in dogs with MUO from 50% to 72%.Conclusions and Clinical ImportanceImaging‐based assessment of BBB integrity has the potential to predict risk of seizures in dogs with MUO.
Keywords:blood‐  brain barrier  epilepsy  meningoencephalitis
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