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Structural Alterations to the Endothelial Tight Junction Complex During Stroke

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Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Ischemic and hemorrhagic stroke cause marked blood–brain barrier (BBB) and neurovascular unit dysfunction in humans and in animal models. The tight junctions (TJs) that link the cerebral endothelial cells are critical for BBB function and they undergo marked modifications after stroke. Those changes contribute to increased BBB permeability, brain edema, and leukocyte infiltration, all hallmarks of stroke. This review describes the types of TJ modifications that occur after stroke (e.g., protein phosphorylation, altered protein/protein interactions, protein relocation, and degradation), the underlying mechanisms and potential therapeutic interventions. While the effects of stroke on the BBB have long been considered as secondary to neuronal injury, increasing evidence stresses the importance of neurovascular injury in stroke and that BBB damage may be a cause rather than a result of stroke-induced parenchymal damage.

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Acknowledgments

This work was supported by grants NS-034709 (R.F.K.), NS-093399 (R.F.K.), NS062853 (A.V.A.), and NS075757 (A.V.A.) from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.

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Authors and Affiliations

  1. Department of Pathology, University of Michigan, 1150 West Medical Center Dr, Ann Arbor, MI, 48109-5602, USA

    Anuska V. Andjelkovic M.D., Ph.D.

  2. Department of Neurosurgery, University of Michigan Health System, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Anuska V. Andjelkovic M.D., Ph.D. & Richard F. Keep Ph.D.

  3. Department of Molecular and Integrative Physiology, University of Michigan, 1150 West Medical Center Dr, Ann Arbor, MI, 48109-5602, USA

    Richard F. Keep Ph.D.

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  1. Anuska V. Andjelkovic M.D., Ph.D.
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Correspondence to Richard F. Keep Ph.D. .

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  1. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Jun Chen

  2. Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    John H. Zhang

  3. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Xiaoming Hu

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Andjelkovic, A.V., Keep, R.F. (2016). Structural Alterations to the Endothelial Tight Junction Complex During Stroke. In: Chen, J., Zhang, J., Hu, X. (eds) Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-32337-4_1

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