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Effects of Endogenous Cannabinoid System In a Mouse Focal Ischemia/Reperfusion Model
Author(s) -
Zhang Ming,
Martin Billy R,
Adler Martin W,
Razdan Raj K,
Tuma Ronald F
Publication year - 2007
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.21.6.a1274-b
Subject(s) - antagonist , cannabinoid , agonist , cannabinoid receptor , medicine , anesthesia , cannabinoid receptor type 2 , ischemia , pharmacology , receptor
The endogenous cannabinoid system, including cannabinoid receptors as well as their native ligands, has been shown to modulate neurotransmission and neuroinflammatory response during cerebral ischemic stroke. The goal of this study is to evaluate the role of activation of specific cannabinoid receptors activation by endocannabinoids in cerebral ischemia/reperfusion injury. Selective CB 1 antagonist, CB 2 antagonist, CB 1 plus CB 2 antagonist, CB 1 antagonist plus CB 2 agonist, CB 2 antagonist plus CB 2 agonist were administered 1 hour before transient middle cerebral artery occlusion (MCAO) in male C57BL/6mice. The antagonists were given at dose of 20mg/kg i.p ., while agonist was given at 1mg/kg i.v. MCAO was performed by an intraluminal filament method for 1 hour followed by 23 hours reperfusion. Cerebral blood flow were continuously monitored during ischemia, infarct volume and neurological deficit were determined 24 hours after MCAO. Administration of CB 1 antagonist significantly decreased cerebral infarction by 46%; CB 2 antagonist increased infarction by 30% while combination of CB 1 and CB 2 antagonists decreased infarction by 24%. The combination of CB 1 antagonist and CB 2 agonist exerted further protection by decreasing infarction by 91% and significantly improved motor function. This project is funded, in part, under a grant with the Pennsylvania Department of Health.