Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2. Issue 6 (June 2021)

• Record Type: Journal Article
• Authors: Kakarla, Visesha; Kaneko, Naoki; Nour, May; Khatibi, Kasra; Elahi, Fanny; Liebeskind, David S; Hinman, Jason D
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 41:Issue 6(2021)
• Page Start: 1179
• Page End: 1192
• Publication Date: 2021-06
• Subjects: Sars-CoV-2 -- stroke -- infection -- inflammation -- endothelia; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X20985666
• Languages: English
• ISSNs: 0271-678X

Abstract

Cerebrovascular events have emerged as a central feature of the clinical syndrome associated with Sars-CoV-2 infection. This increase in infection-related strokes is marked by atypical presentations including stroke in younger patients and a high rate of hemorrhagic transformation after ischemia. A variety of pathogenic mechanisms may underlie this connection. Efforts to identify synergism in the pathophysiology underlying stroke and Sars-CoV-2 infection can inform the understanding of both conditions in novel ways. In this review, the molecular cascades connected to Sars-CoV-2 infection are placed in the context of the cerebral vasculature and in relationship to pathways known to be associated with stroke. Cytokine-mediated promotion of systemic hypercoagulability is suggested while direct Sars-CoV-2 infection of cerebral endothelial cells may also contribute. Endotheliopathy resulting from direct Sars-CoV-2 infection of the cerebral vasculature can modulate ACE2/AT1 R/MasR signaling pathways, trigger direct viral activation of the complement cascade, and activate feed-forward cytokine cascades that impact the blood-brain barrier. All of these pathways are already implicated as independent mechanisms driving stroke and cerebrovascular injury irrespective of Sars-CoV-2. Recognizing the overlap of molecular pathways triggered by Sars-CoV-2 infection with those implicated in the pathogenesis of stroke provides an opportunity to identify future therapeutics targeting both Sars-CoV-2 and stroke thereby reducing the impact of the global pandemic.