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Development, maintenance and disruption of the blood-brain barrier

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Abstract

The interface between the blood circulation and the neural tissue features unique characteristics that are encompassed by the term 'blood-brain barrier' (BBB). The main functions of this barrier, namely maintenance of brain homeostasis, regulation of influx and efflux transport, and protection from harm, are determined by its specialized multicellular structure. Every constituent cell type makes an indispensable contribution to the BBB's integrity. But if one member of the BBB fails, and as a result the barrier breaks down, there can be dramatic consequences and neuroinflammation and neurodegeneration can occur. In this Review, we highlight recently gained mechanistic insights into the development and maintenance of the BBB. We then discuss how BBB disruption can cause or contribute to neurological disease. Finally, we examine how this knowledge can be used to explore new possibilities for BBB repair.

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Figure 1: Cellular interplay at the neurovascular unit (capillary level).
Figure 2: Major signaling pathways in BBB development.
Figure 3: Central role of pericytes in the neurovascular unit.
Figure 4: Causes, characteristics and consequences of BBB breakdown.
Figure 5: Pathogenic mechanisms of epilepsy and neuromyelitis optica.

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Acknowledgements

R.M.R. is supported by US National Insititutes of Health grant R21 NS074820 and the Guthy Jackson Charitable Foundation. R.D. is supported by the Program for Breakthrough Biomedical Sciences and the American Heart Association. B.O. is supported by a two-year Research Fellowship from the Deutsche Forschungsgemeinschaft.

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Obermeier, B., Daneman, R. & Ransohoff, R. Development, maintenance and disruption of the blood-brain barrier. Nat Med 19, 1584–1596 (2013). https://doi.org/10.1038/nm.3407

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