Increased severity of stroke in CB1 cannabinoid receptor knock-out mice.
Endogenous cannabinoid signaling pathways have been implicated in protection of the brain from hypoxia, ischemia, and trauma, but the mechanism for these protective effects is uncertain. We found that in CB1 cannabinoid receptor knock-out mice, mortality from permanent focal cerebral ischemia was increased, infarct size and neurological deficits after transient focal cerebral ischemia were more severe, cerebral blood flow in the ischemic penumbra during reperfusion was reduced, and NMDA neurotoxicity was increased compared with wild-type littermates. These findings indicate that endogenous cannabinoid signaling pathways protect mice from ischemic stroke by a mechanism that involves CB1 receptors, and suggest that both blood vessels and neurons may be targets of this protective effect.
Parmentier-Batteur
Sophie
S
Buck Institute for Age Research, Novato, California 94945, USA.
Jin
Kunlin
K
Mao
Xiao Ou
XO
Xie
Lin
L
Greenberg
David A
DA
D000818:Animals; D001783:Blood Flow Velocity / Q000235:genetics; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000235:genetics; D004195:Disease Models, Animal; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000172:deficiency* / Q000235:genetics; D015424:Reperfusion; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology*; D015996:Survival Rate
D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D016202:N-Methylaspartate