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Anandamide content is increased and CB1 cannabinoid receptor blockade is protective during transient, focal cerebral ischemia. Neuroscience 2004;129(3):743-50

Date

11/16/2004

Pubmed ID

15541895

DOI

10.1016/j.neuroscience.2004.08.044

Scopus ID

2-s2.0-8444250235 (requires institutional sign-in at Scopus site)   127 Citations

Abstract

The role of endocannabinoid signaling in the response of the brain to injury is tantalizing but not clear. In this study, transient middle cerebral artery occlusion (MCAo) was used to produce ischemia/reperfusion injury. Brain content of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol were determined during MCAo. Whole brain AEA content was significantly increased after 30, 60 and 120 min MCAo compared with sham-operated brain. The increase in AEA was localized to the ischemic hemisphere after 30 min MCAo, but at 60 and 120 min, was also increased in the contralateral hemisphere. 2-Arachidonoylglycerol content was unaffected by MCAo. In a second set of studies, injury was assessed 24 h after 2 h MCAo. Rats administered a single dose (3 mg/kg) of the cannabinoid receptor type 1 (CB1) receptor antagonist SR141716 prior to MCAo exhibited a 50% reduction in infarct volume and a 40% improvement in neurological function compared with vehicle control. A second CB1 receptor antagonist, LY320135 (6 mg/kg), also significantly improved neurological function. The CB1 receptor agonist, WIN 55212-2 (0.1-1 mg/kg) did not affect either infarct volume or neurological score.

Author List

Muthian S, Rademacher DJ, Roelke CT, Gross GJ, Hillard CJ

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acids
Benzofurans
Benzoxazines
Blood Pressure
Brain Chemistry
Brain Infarction
Chromatography, Liquid
Disease Models, Animal
Dose-Response Relationship, Drug
Endocannabinoids
Hemodynamics
Infarction, Middle Cerebral Artery
Ischemic Attack, Transient
Male
Mass Spectrometry
Morpholines
Naphthalenes
Neurologic Examination
Piperidines
Polyunsaturated Alkamides
Pyrazoles
Rats
Rats, Wistar
Receptor, Cannabinoid, CB1
Reperfusion Injury
Tetrazolium Salts
Time Factors