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The increasing incidence of large vessel ischemic strokes as well as intracranial hemorrhages, frequently in younger individuals, and associated with increased morbidity and mortality, has raised questions as to why the brain is a major target of the disease. COVID-19 is characterized by hypercoagulability with alterations in hemostatic markers including high D-dimer levels, which are a prognosticator of poor outcome. Together with findings of fibrin-rich microthrombi, widespread extracellular fibrin deposition in affected various organs and hypercytokinemia, this suggests that COVID-19 is more than a pulmonary viral infection. Evidently, COVID-19 is a thrombo-inflammatory disease. Endothelial cells that constitute the lining of blood vessels are the primary targets of a thrombo-inflammatory response, and severe acute respiratory syndrome coronavirus 2 also directly infects endothelial cells through the ACE2 (angiotensin-converting enzyme 2) receptor. Being highly heterogeneous in their structure and function, differences in the endothelial cells may govern the susceptibility of organs to COVID-19. Here, we have explored how the unique characteristics of the cerebral endothelium may be the underlying reason for the increased rates of cerebrovascular pathology associated with COVID-19.<\/jats:p>","DOI":"10.1161\/strokeaha.120.032711","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T05:00:26Z","timestamp":1617339626000},"page":"1895-1904","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Endothelial Dysfunction in the Brain"],"prefix":"10.1161","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9712-4784","authenticated-orcid":true,"given":"Maithili","family":"Sashindranath","sequence":"first","affiliation":[{"name":"Australian Centre for Blood Diseases, Central Clinical School, Monash University and Alfred Health, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshal H.","family":"Nandurkar","sequence":"additional","affiliation":[{"name":"Australian Centre for Blood Diseases, Central Clinical School, Monash University and Alfred Health, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 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