[Neuroprotective effect of preconditioning with cannabinoid receptor agonist WIN 55, 212 - 2 on focal cerebral ischemia: experiment with rats].
OBJECTIVE
To investigate the neuroprotective effect of preconditioning with cannabinoid (CB) receptor agonist WIN 55, 212 - 2 on focal cerebral ischemia.


METHODS
Fifty male SD rats were randomly assigned to 5 equal groups: control group undergoing middle cerebral artery occlusion (MCAO) for 2 h only without any preconditioning; 3 WIN 55, 212 - 2 preconditioning groups (WIN1-3) injected intraperitoneally with WIN 55, 212 - 2 at the doses of 0.3, 1, and 3 mg/kg respectively 24 h before MCAO for 2 h, and DMSO group injected intraperitoneally with dimethyl sulfoxide (DMSO), solvent of WIN 55, 212 - 2 24 h before MCAO for 2 h. 24, 48, and 72 hours after reperfusion the neurological function score (NFS) was evaluated the rats were then decapitated with their brains taken out. Brain infarct volume was evaluated with 2% 2, 3, 5-triphenyltetrazolium chloride (TTC) staining.


RESULTS
The NFS values of the rats in WIN 55, 212 - 2 preconditioning groups were all significantly higher than those of the control and DMSO groups (all P < 0.05) while the infarct volumes of the WIN 55, 212 - 2 preconditioning groups were all significantly smaller than those of the control and DMSO groups (all P < 0.05) 24, 48, and 72 h after reperfusion. The infarct volumes of the WIN2 and WIN3 groups were both significantly smaller than that of the WIN1 group (both P < 0.05). However, there was no significant difference in the infarct volume between WIN2 and WIN3 groups (P = 0.928).


CONCLUSIONS
WIN 55, 212 - 2 preconditioning has neuroprotective effect on focal cerebral ischemia with a dose-dependent manner.
Chen
Ye
Y
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Chen
Shao-yang
SY
Wang
Qiang
Q
Sun
Jing
J
Zhu
Zheng-hua
ZH
Hou
Li-chao
LC
Xiong
Li-ze
LZ
D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D063386:Cannabinoid Receptor Agonists; D020244:Infarction, Middle Cerebral Artery / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D009281:Naphthalenes / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone