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Anatomy and Physiology of the Blood–Brain Barriers

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 10))

Abstract

This chapter covers the three main barrier layers separating blood and the central nervous system (CNS): the endothelium of the brain vasculature, the epithelium of the choroid plexus secreting cerebrospinal fluid (CSF) into the ventricles and the arachnoid epithelium forming the middle layer of the meninges on the brain surface. There are three key barrier features at each site that control the composition of brain fluids and regulate CNS drug permeation: (1) physical barriers result from features of the cell membranes and of the tight junctions restricting the paracellular pathway through intercellular clefts; (2) transport barriers result from membrane transporters mediating solute uptake and efflux, together with vesicular mechanisms mediating transcytosis of larger molecules such as peptides and proteins and (3) enzymatic barriers result from cell surface and intracellular enzymes that can modify molecules in transit. Brain fluids (CSF and brain interstitial fluid) are secreted, flow through particular routes and then drain back into the venous system; this fluid turnover aids central homeostasis and also affects CNS drug concentration. Several CNS pathologies involve changes in the barrier layers and the fluid systems. Many of these aspects of physiology and pathology have implications for drug delivery.

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Acknowledgements

I am grateful to Dr Siti R. Yusof for help with artwork and many colleagues for discussions.

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Authors and Affiliations

  1. Institute of Pharmaceutical Science, Blood–Brain Barrier Group, King’s College London, Franklin Wilkins Building 3.10, 150 Stamford Street, London, SE1 9NH, UK

    N. Joan Abbott

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Correspondence to N. Joan Abbott .

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Editors and Affiliations

  1. Pharmaceutical Biosciences, Uppsala University Pharmacokinetics and Drug Therapy, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  2. LACDR/Pharmacology, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  3. Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin, USA

    Robert G. Thorne

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Abbott, N.J. (2014). Anatomy and Physiology of the Blood–Brain Barriers. In: Hammarlund-Udenaes, M., de Lange, E., Thorne, R. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9105-7_1

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