Role of Protease-Activated Receptor-1 in Brain Injury After Experimental Global Cerebral Ischemia
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.
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.
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.
Conclusion—PAR-1 contributes to the brain injury induced by global cerebral ischemia, which may be related to activation of mitogen-activated protein kinases.
- brain edema
- global cerebral ischemia
- mitogen-activated protein kinases
- protease activated receptor-1 (PAR-1)
- Received April 20, 2012.
- Revision received May 15, 2012.
- Accepted June 1, 2012.
- © 2012 American Heart Association, Inc.