Background and purpose
Evidence suggests that the protease-activated receptor-1 (PAR-1), a thrombin receptor, mediates neuronal injury in experimental cerebral ischemia. The present study investigated whether PAR-1 plays a role in brain injury after global cerebral ischemia.
Conclusions
PAR-1 contributes to the brain injury induced by global cerebral ischemia, which may be related to activation of mitogen-activated protein kinases.
Methods
Adult male wild-type or PAR-1 knockout mice underwent a 20-minute bilateral common carotid artery occlusion or a sham operation. Behavior tests were performed before ischemia and 1, 2, and 3 days after bilateral common carotid artery occlusion. Mice were euthanized at different time points for thrombin activity, brain edema, Western blot analysis, and brain histology.
Purpose
Evidence suggests that the protease-activated receptor-1 (PAR-1), a thrombin receptor, mediates neuronal injury in experimental cerebral ischemia. The present study investigated whether PAR-1 plays a role in brain injury after global cerebral ischemia.
Results
Thrombin activity and PAR-1 expression were increased in the brain after bilateral common carotid artery occlusion. Compared with wild-type mice, PAR-1 knockout mice had less brain edema formation, neuronal death, and behavior impairment after bilateral common carotid artery occlusion. In addition, bilateral common carotid artery occlusion-induced activation of mitogen-activated protein kinases was absent in PAR-1 knockout mice. Conclusions: PAR-1 contributes to the brain injury induced by global cerebral ischemia, which may be related to activation of mitogen-activated protein kinases.