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Targeting Pericytes and the Microcirculation for Ischemic Stroke Therapy

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Neuroprotective Therapy for Stroke and Ischemic Disease

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

Abstract

Ischaemic stroke is a major global cause of disability and death, yet the therapeutic options currently available for stroke are very limited. The only effective acute treatments of ischemic stroke revolve around restoring patency to the occluded artery through degradation (intravenous thrombolysis) or mechanical removal of the clot [Int J Stroke 10:1168–1178, 2015; Brain 136:3528–3553, 2013]. However, there is an increasing body of evidence to suggest that even following recanalization of the large vessel, the post-ischemic microvasculature remains dysfunctional and does not necessarily allow effective reperfusion. Contributors to this phenomenon include astrocyte swelling and compression of microvessels, obstruction of flow due to inflammatory changes, leukocyte adhesion and thrombosis, and the constriction of capillaries by pericytes dying in rigor [Shock 8:95–101, 1997; J Cereb Blood Flow 36:451–455, 2016]. This chapter will provide an overview of microvascular function in health, describe the pathological changes that occur following ischemia and reperfusion, and explore the role of the microvasculature, with a focus on pericytes as a potential therapeutic target in ischemic stroke.

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Acknowledgments

The authors thank Dr. Hasneen Karbalai for his constructive comments on the manuscript. The authors were supported by funding from the Radcliffe Department of Medicine Scholarship (AAN), Medical Research Council (AMB, BAS), and Oxford Biomedical Research Centre (AMB).

Disclosures AMB is a cofounder of Brainomix Limited, a start-up company from the University of Oxford developing imaging biomarkers for neurological and cerebrovascular disorders.

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Authors and Affiliations

  1. Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    Ain A. Neuhaus M.A., Brad A. Sutherland Ph.D. & Alastair M. Buchan DSc (Oxon) LLD (Hon) FRCP FRCPEd

  2. School of Medicine, University of Tasmania, Hobart, Australia

    Brad A. Sutherland Ph.D.

  3. Medical Sciences Division, University of Oxford, Level 3, John Radcliffe Hospital, Headley Way, Oxford, Oxfordshire, OX3 9DU, UK

    Alastair M. Buchan DSc (Oxon) LLD (Hon) FRCP FRCPEd

  4. Acute Vascular Imaging Centre, University of Oxford, Oxford University Hospitals, Oxford, UK

    Alastair M. Buchan DSc (Oxon) LLD (Hon) FRCP FRCPEd

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  1. Ain A. Neuhaus M.A.
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  2. Brad A. Sutherland Ph.D.
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  3. Alastair M. Buchan DSc (Oxon) LLD (Hon) FRCP FRCPEd
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Correspondence to Alastair M. Buchan DSc (Oxon) LLD (Hon) FRCP FRCPEd .

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Editors and Affiliations

  1. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Paul A. Lapchak

  2. Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

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Neuhaus, A.A., Sutherland, B.A., Buchan, A.M. (2017). Targeting Pericytes and the Microcirculation for Ischemic Stroke Therapy. In: Lapchak, P., Zhang, J. (eds) Neuroprotective Therapy for Stroke and Ischemic Disease. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45345-3_22

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