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PAR4 Deficiency Inhibits Microvascular Inflammation after Cerebral Ischemia/Reperfusion Injury
Author(s) -
Mao Yingying,
Zhang Ming,
Kunapuli Satya,
Tuma Ronald
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.590.11
Subject(s) - medicine , ischemia , inflammation , stroke (engine) , reperfusion injury , platelet , thrombin , blood–brain barrier , intravital microscopy , cerebral edema , anesthesia , edema , pharmacology , endothelium , central nervous system , immunology , microcirculation , mechanical engineering , engineering
Stroke is the second leading cause of death worldwide and antithrombotic therapy targeting thrombin signaling is one of the new treatments for ischemic stroke. Protease‐activated receptor 4 (PAR4) is the major thrombin receptors expressed in murine platelets. The role of PAR4 in cerebral ischemia/reperfusion injury was investigated by using a mouse transient middle cerebral artery occlusion/reperfusion (MCAO/R) model. Platelet/endothelial and leukocyte/endothelial interactions, which have been shown to play a critical role in the inflammatory responses during cerebral ischemic/reperfusion injury, were studied via a cranial window and intravital microscopy. We demonstrated that PAR4 −/− mice had a significant reduction in infarct volume at both 24 hours at 48 hours (p<0.001) following 1 hour MCAO compare to wild‐type mice. Furthermore, deficiency of PAR4 significantly decreased both platelet/endothelial and leukocyte/endothelial interactions. In addition, we also found that blood‐brain barrier (BBB) disruption and edema formation were dramatically attenuated in PAR4−/− mice. In conclusion, PAR4 deficiency protects against cerebral ischemic injury partially though attenuation of cerebral microvascular inflammation. Therefore, PAR4 may represent therapeutic target for the treatment ischemia injury.