Targeting Pericytes and the Microcirculation for Ischemic Stroke Therapy

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.