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. CONCLUSIONS: PAR-1 contributes to the brain injury induced by global cerebral ischemia, which may be related to activation of mitogen-activated protein kinases.
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. CONCLUSIONS:PAR-1 contributes to the brain injury induced by global cerebral ischemia, which may be related to activation of mitogen-activated protein kinases.
Authors: Petra Henrich-Noack; Monika Riek-Burchardt; Kathrin Baldauf; Georg Reiser; Klaus G Reymann Journal: Brain Res Date: 2006-01-03 Impact factor: 3.252
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Authors: D Isaev; I Lushnikova; O Lunko; O Zapukhliak; O Maximyuk; A Romanov; G G Skibo; C Tian; G L Holmes; E Isaeva Journal: Neurobiol Dis Date: 2015-04-02 Impact factor: 5.996
Authors: Afolabi C Akinmoladun; Bolanle L Akinrinola; M Tolulope Olaleye; Ebenezer O Farombi Journal: Neurochem Res Date: 2015-02-01 Impact factor: 3.996