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The Blood-Brain Barrier in Stroke and Trauma and How to Enhance Drug Delivery

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 33))

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Abstract

Ischemic or hemorrhagic stroke and traumatic brain injury (TBI) cause marked changes in blood-brain barrier (BBB) function. Such changes increase barrier permeability and induce vasogenic edema and leukocyte extravasation into the brain. In addition, BBB dysfunction affects the entry of therapeutics into the brain. This chapter describes changes in BBB function after brain injury, how stroke and TBI affect drug delivery, the BBB as a therapeutic target, and enhancing drug delivery in stroke and TBI.

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Abbreviations

AAVs:

adeno-associated viruses

ABC transporters:

ATP-binding cassette transporters

BBB:

blood-brain barrier

BDNF:

brain-derived neurotrophic factor

bFGF:

basic fibroblast growth factor

CBF:

cerebral blood flow

CSF:

cerebrospinal fluid

Gd-DPTA:

gadolinium-diethylenetriaminepentacetate

ICH:

intracerebral hemorrhage

Nrf2:

nuclear factor erythroid 2-related factor 2

NVU:

neurovascular unit

Oat3:

organic anion transporter-3

PS product:

permeability surface area product

SAH:

subarachnoid hemorrhage

shRNA:

short hairpin RNA

SVCT2:

Na-dependent vitamin C transporter 2

TBI:

traumatic brain injury

TJ:

tight junction

tPA:

tissue plasminogen activator

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Richard F. Keep, Jianming Xiang & Anuska V. Andjelkovic

  2. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

    Richard F. Keep

  3. Department of Pharmacology, Yunnan University of Traditional Chinese Medicine, Kunming, China

    Ningna Zhou

  4. Department of Pathology, University of Michigan, Ann Arbor, MI, USA

    Anuska V. Andjelkovic

Authors
  1. Richard F. Keep
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  2. Jianming Xiang
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  3. Ningna Zhou
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  4. Anuska V. Andjelkovic
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Corresponding author

Correspondence to Richard F. Keep .

Editor information

Editors and Affiliations

  1. Research Division of Systems Pharmacology and Pharmacy, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  2. Department of Pharmacy, Uppsala University, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  3. Biology Discovery, Denali Therapeutics, South San Francisco, CA, USA

    Robert G. Thorne

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Keep, R.F., Xiang, J., Zhou, N., Andjelkovic, A.V. (2022). The Blood-Brain Barrier in Stroke and Trauma and How to Enhance Drug Delivery. In: de Lange, E.C., Hammarlund-Udenaes, M., Thorne, R.G. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 33. Springer, Cham. https://doi.org/10.1007/978-3-030-88773-5_23

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