12/11/2023 0 Comments Google sketchup 2020![]() All rights reserved.ĪCE2 is expressed on the cerebral vasculature and in primary human brain microvascular endothelial cells (hBMVECs). Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.īlood-brain barrier COVID-19 Cerebral vascular biology Microfluidic chip Neuroinflammation SARS-CoV-2 Tissue engineering.Ĭopyright © 2020 The Author(s). Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. ![]() Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface. Introduction of spike proteins to invitro models of the blood-brain barrier (BBB) showed significant changes to barrier properties. Analysis of cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48 h exposure window. ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions. Moreover, ACE2 expression was upregulated in cases of hypertension and dementia. ![]() First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is ubiquitously expressed throughout various vessel calibers in the frontal cortex. The spike protein, which plays a key role in receptor recognition, is formed by the S1 subunit containing a receptor binding domain (RBD) and the S2 subunit. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. Electronic address: researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. 4 Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, United States of America Center for Substance Abuse Research, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, United States of America The Shriners Hospitals Pediatric Research Center, Philadelphia, PA 19140, United States of America.3 Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, United States of America.2 Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, United States of America.1 Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, United States of America Center for Substance Abuse Research, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, United States of America.
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