[Neuroprotective effect of preconditioning with cannabinoid receptor agonist WIN 55, 212 - 2 on focal cerebral ischemia: experiment with rats]

Zhonghua Yi Xue Za Zhi. 2008 Aug 12;88(31):2219-22.
[Article in Chinese]

Abstract

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).

Conclusion: WIN 55, 212 - 2 preconditioning has neuroprotective effect on focal cerebral ischemia with a dose-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines / administration & dosage
  • Benzoxazines / therapeutic use*
  • Brain / blood supply
  • Brain / drug effects
  • Brain / pathology
  • Brain Ischemia / prevention & control*
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / therapeutic use
  • Cannabinoid Receptor Agonists*
  • Infarction, Middle Cerebral Artery / prevention & control
  • Injections, Intraperitoneal
  • Ischemic Preconditioning / methods*
  • Male
  • Morpholines / administration & dosage
  • Morpholines / therapeutic use*
  • Naphthalenes / administration & dosage
  • Naphthalenes / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control

Substances

  • Benzoxazines
  • Calcium Channel Blockers
  • Cannabinoid Receptor Agonists
  • Morpholines
  • Naphthalenes
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone