Endothelial cell, astrocyte, and BBB interface. (IMAGE)
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The connection between perturbations in BBB barrier function and damage to the astrocyte network and its functions arises from BBB damage, leading to the extravasation of albumin. In the physiological state, tight junctions of endothelial cells maintain the integrity of the BBB, preventing the infiltration of albumin from the circulation into the central nervous system (CNS). Pericytes regulate vascular constriction. Within the brain-wide perivascular space, a polarized astrocyte phenotype with AQP4 expression is essential for the functioning of the glymphatic system. When the BBB is disrupted, astrocytes are exposed to albumin from the serum. This exposure triggers the mediation of albumin uptake by astrocytes through the TGF-βR. Activation of the TGF-β pathway results in elevated levels of IL-6 and the onset of neuroinflammation. Simultaneously, endothelial cells release PGE2, which enhances astrocytic Ca2+ levels via the EP3 receptor.
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