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Leakage at Blood-Neural Barriers

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The Blood Brain Barrier and Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Permeability of blood vessels in the brain and retina is usually very low and dominated by the restricting properties of the blood-brain and blood-retinal barriers, respectively. The highly specialised endothelium pervading the brain and the retina displays low permeability due to the nearly complete absence of transcellular transport (with the exception of that of specific nutrients and metabolites) and also to highly differentiated tight junctions. Importantly, the neuroglial cells that are part of cerebral and retinal blood vessels appear to be the main driver for inducing and maintaining these specialised properties of the endothelium. During many traumatic, inflammatory or degenerative neuro- and retinopathologies, this neurovascular unit is compromised leading to reduced vascular endothelial barrier properties and detrimental leakage of blood components into nervous tissue. Importantly, many extracellular permeability-inducing factors such as histamines, kinins, growth factors and lipids can trigger endothelial leakage in varying ways, but in most cases, pathological leakage occurs through consecutive or parallel opening of the paracellular space (characterised by tight junction protein loss) and induction of transcellular vesicles (possibly caveolae). Both pathways are regulated by complex often overlapping protein phosphorylation and GTPase networks, which lends credence to efforts to limit leakage at the BBB and BRB by specific signalling antagonists. Finally, leakage pathways are also exploited to facilitate drug delivery to the brain.

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Acknowledgements

The author would like to thank Prof John Greenwood for stimulating discussions over the past 15 years and for critically reviewing this manuscript.

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  1. Cell Biology, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK

    Patric Turowski

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  1. Theodor Kocher Institute, University of Bern, Bern, Switzerland

    Ruth Lyck

  2. Theodor Kocher Institute, University of Bern, Bern, Switzerland

    Gaby Enzmann

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Turowski, P. (2017). Leakage at Blood-Neural Barriers. In: Lyck, R., Enzmann, G. (eds) The Blood Brain Barrier and Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45514-3_5

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