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

Abstract

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 (PAR₁) in cerebral vasospasm was investigated using a rabbit double hemorrhage SAH model. The expression of PAR₁ was up-regulated and the contractile response to thrombin was markedly enhanced in the basilar artery of SAH models. The intrathecal administration of a PAR₁ antagonist prevented the up-regulation of PAR₁ and the enhancement of the contractile responses to thrombin in SAH. These observations thus suggest that PAR₁ may play a pivotal role in post-hemorrhagic cerebral vasospasm in SAH. Following SAH, thrombin activates PAR₁, thereby up-regulating the expression of PAR₁, which culminates in the increased contractile response to thrombin in the basilar artery. PAR₁ antagonists are thus anticipated to be a novel therapeutic strategy for cerebral vasospasm. However, further studies are needed before establishing the clinical usefulness of PAR₁ antagonists.