"Introduction
... In the present study, a three-dimensional model of the blood–brain barrier (BBB) was utilized to examine the role of ACE2 and SARS-CoV-2 spike protein on BBB homeostasis. The model employs human cerebral microvascular endothelial cells in combination with fluid shear stress in a collagen/HA [hyaluronic acid] hydrogel matrix in order to mimic the human BBB. This platform enables the real time assessment of BBB function in response to spike protein such as permeability and transendothelial electrical resistance (TEER) measurements...
Discussion
The results presented here provide preliminary insight into the mechanisms underlying the effect of the SARS-CoV-2 spike protein on barrier integrity and identify RhoA [Ras homolog family member A] as a key mediator of spike-induced barrier disruption... when brain endothelial cells are exposed to the S1 subunit of the spike protein in the presence of fluid shear stress, expression of ACE2 is upregulated to static levels...
ELISA assays indicated that S1 spike protein significantly increased the activation of RhoA, demonstrating that the small GTPase [guanosine triphosphatase] influences barrier breakdown in response to SARS-CoV-2. The activation of RhoA has been shown to induce cell contractility and cytoskeleton restructuring, resulting in enhanced cell motility and disrupted barrier integrity."
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