Neurocoagulation from a Mechanistic Point of View in the Central Nervous System.

Coagulation mechanisms are critical for maintaining homeostasis in the central nervous system (CNS). Thrombin, an important player of the coagulation cascade, activates protease activator receptors (PARs), members of the G-protein coupled receptor family. PAR1 is located on neurons and glia. Following thrombin activation, PAR1 signals through the extracellular signal-regulated kinase pathway, causing alterations in neuronal glutamate release and astrocytic morphological changes. Similarly, the anticoagulation factor activated protein C (aPC) can cleave PAR1, following interaction with the endothelial protein C receptor. Both thrombin and aPC are expressed on endothelial cells and pericytes in the blood-brain barrier (BBB). Thrombin-induced PAR1 activation increases cytosolic Ca

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