Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2

Visesha Kakarla, Naoki Kaneko, May Nour, Kasra Khatibi, Fanny Elahi, David S. Liebeskind, Jason D. Hinman

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

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/AT1R/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.

Original languageEnglish
Pages (from-to)1179-1192
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume41
Issue number6
DOIs
StatePublished - Jun 2021
Externally publishedYes

Keywords

  • Sars-CoV-2
  • endothelia
  • infection
  • inflammation
  • stroke

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