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Fluids and Barriers of the CNS

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Open Access 01-12-2013 | Study protocol

Organotypic brain slices: a model to study the neurovascular unit micro-environment in epilepsies

Authors: Mélanie Morin-Brureau, Frédéric De Bock, Mireille Lerner-Natoli

Published in: Fluids and Barriers of the CNS | Issue 1/2013

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.

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Title: Organotypic brain slices: a model to study the neurovascular unit micro-environment in epilepsies
Authors: Mélanie Morin-Brureau
Frédéric De Bock
Mireille Lerner-Natoli
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Fluids and Barriers of the CNS / Issue 1/2013
Electronic ISSN: 2045-8118
DOI: https://doi.org/10.1186/2045-8118-10-11

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Organotypic brain slices: a model to study the neurovascular unit micro-environment in epilepsies

Abstract

Background

Methods/design

Discussion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods/design

Discussion

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