Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage

概要

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Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage (SAH). The prevention and treatment of cerebral vasospasm thus plays a critical role in the management of SAH patients. However, the mechanism of cerebral vasospasm still remains elusive, while effective therapeutic strategies also remain to be established. The role of thrombin and its receptor proteinase-activated receptor 1 (PAR_1) in cerebral vasospasm was investigated using a rabbit double hemorrhage SAH model. The expression of PAR_1 was up-regulated and the contractile response to thrombin was markedly enhanced in the basilar artery of SAH models. The intrathecal administration of a PAR_1 antagonist prevented the up-regulation of PAR_1 and the enhancement of the contractile responses to thrombin in SAH. These observations thus suggest that PAR_1 may play a pivotal role in post-hemorrhagic cerebral vasospasm in SAH. Following SAH, thrombin activates PAR_1, thereby up-regulating the expression of PAR_1, which culminates in the increased contractile response to thrombin in the basilar artery. PAR_1 antagonists are thus anticipated to be a novel therapeutic strategy for cerebral vasospasm. However, further studies are needed before establishing the clinical usefulness of PAR_1 antagonists.
Japanese Pharmacological Society,日本薬理学会の論文
2008-12-20