Role of protease-activated receptor-1 in brain injury after experimental global cerebral ischemia.
OBJECTIVE
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.
Department of Neurosurgery, Room 5018 BSRB, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Jinhu
J
Wang
Hang
H
Jin
Ya
Y
Hua
Richard F
RF
Keep
Guohua
G
Xi
D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001834:Body Water / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology* / Q000523:psychology; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053580:Muscle Strength / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D044463:Receptor, PAR-1 / Q000235:genetics / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism
D001786:Blood Glucose; D044463:Receptor, PAR-1; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin