title: The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective?
abstract: In the last two decades it has become apparent that thrombin has many extravascular effects that are mediated by a family of protease-activated receptors (PARs). PAR-1, -3 and -4 are activated via cleavage by thrombin. The importance of extravascular thrombin in modulating ischemic, hemorrhagic and traumatic injury in brain has recently become clear. Thus, in vitro, thrombin at low concentration protects neurons and astrocytes from cell death caused by a number of different insults. In vivo, pretreating the brain with a low dose of thrombin (thrombin preconditioning), attenuates the brain injury induced by a large dose of thrombin, an intracerebral hemorrhage or by focal cerebral ischemia. Thrombin may also be an important mediator of ischemic preconditioning. In contrast, high doses of thrombin kill neurons and astrocytes in vitro and cause disruption of the blood-brain barrier, brain edema and seizures in vivo. This review examines the role of thrombin in brain injury and the molecular mechanisms and signaling cascades involved.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.forename: Georg
authors.initials: G
authors.lastname: Reiser
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000503:physiopathology*; D006801:Humans; D018179:Receptors, Thrombin / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*
chemical_list: D018179:Receptors, Thrombin; D013917:Thrombin