Effects of cannabinoid receptor agonist WIN 55,212-2 on blood-brain barrier disruption in focal cerebral ischemia in rats

This study was performed to investigate whether WIN 55,212-2 (WIN), a cannabinoid receptor agonist, could attenuate blood-brain barrier (BBB) disruption in focal cerebral ischemia in rats and whether the CB₁ receptor antagonist rimonabant could prevent this attenuation. A total of 0.3 or 1 mg/kg of WIN was injected intravenously before and after permanent middle cerebral artery (MCA) occlusion. Some animals were pretreated with rimonabant 2 mg/kg i.p. before receiving 0.3 mg/kg of WIN. At 1 h after MCA occlusion, BBB permeability was determined by measuring the transfer coefficient (K _i) of ¹⁴C-α-aminoisobutyric acid and the volume of dextran distribution. With MCA occlusion, K_i increased in the ischemic cortex (IC) in all of the experimental groups. However, the K _i of the IC of the WIN 0.3 and 1 mg/kg groups was lower (-46 and -42%, respectively, p < 0.05) than that of the control group. With rimonabant pretreatment, the K_i of the IC became higher (+88%, p < 0.05) than with WIN 0.3 mg/kg alone and similar to that of the control rats. The difference in the volume of dextran distribution between the IC and the contralateral cortex was significant in the control but not in the WIN-treated rats. With rimonabant pretreatment, however, the difference became significant. Our data demonstrated that WIN could attenuate BBB disruption in focal cerebral ischemia and this attenuation could be prevented with rimonabant. Our data suggest an involvement of CB₁ receptors in the regulation of BBB disruption in the early stage of stroke.