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- W2105412757 abstract "Abstract Background It is now recognized that the neuro-vascular unit (NVU) plays a key role in several neurological diseases including epilepsy, stroke, Alzheimer’s disease, multiple sclerosis and the development of gliomas. Most of these disorders are associated with NVU dysfunction, due to overexpression of inflammatory factors such as vascular endothelial growth factor (VEGF). Various in vitro models have been developed previously to study the micro-environment of the blood–brain barrier (BBB). However none of these in vitro models contained a complete complement of NVU cells, nor maintained their interactions, thus minimizing the influence of the surrounding tissue on the BBB development and function. The organotypic hippocampal culture (OHC) is an integrative in vitro model that allows repeated manipulations over time to further understand the development of cell circuits or the mechanisms of brain diseases. Methods/design OHCs were cultured from hippocampi of 6–7 day-old Sprague Dawley rats. After 2 weeks in culture, seizures were induced by application of kainate or bicuculline into culture medium. The regulation of BBB integrity under physiological and pathological conditions was evaluated by immunostaining of the main tight junction (TJ) proteins and of the basal membrane of microvessels. To mimic or prevent BBB disassembly, we used diverse pro- or anti-angiogenic treatments. Discussion This study demonstrates that NVU regulation can be investigated using OHCs. We observed in this model system an increase in vascularization and a down-regulation of TJ proteins, similar to the vascular changes described in a chronic focus of epileptic patients, and in rodent models of epilepsy or inflammation. We observed that Zonula occludens-1 (ZO-1) protein disappeared after seizures associated with neuronal damage. In these conditions, the angiopoeitin-1 system was down-regulated, and the application of r-angiopoeitin-1 allowed TJ re-assembly. This article demonstrates that organotypic culture is a useful model to decipher the links between epileptic activity and vascular damage, and also to investigate NVU regulation in diverse neurological disorders." @default.
- W2105412757 created "2016-06-24" @default.
- W2105412757 creator A5004637139 @default.
- W2105412757 creator A5057049609 @default.
- W2105412757 creator A5075314368 @default.
- W2105412757 date "2013-02-07" @default.
- W2105412757 modified "2023-10-16" @default.
- W2105412757 title "Organotypic brain slices: a model to study the neurovascular unit micro-environment in epilepsies" @default.
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- W2105412757 doi "https://doi.org/10.1186/2045-8118-10-11" @default.
- W2105412757 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3605299" @default.
- W2105412757 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23391266" @default.
- W2105412757 hasPublicationYear "2013" @default.
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