Combined neuroprotective action of JWH-015 and AM251 in the CA1 hippocampal area of transient global cerebral ischemia

Transient global cerebral ischemia (TGCI) induces by bilateral common carotid artery occlusion (BCCAO), and it mediates neuronal cell death of the CA1 hippocampal area. AM251 is a cannabinoid receptors type 1 (CB1) blocker that has been known to be protective against transient focal cerebral ischemia. JWH-015 is a selective agonist of CB2 and activator of CB1 that is involved in promotion of neuronal recovery and survival. The role of combined application of JWH-015 with AM251 in the rat model of GCI has been surveyed in this study. Male Wistar rats underwent 20 min of ischemia followed by reperfusion. Then, 1 mg/kg JWH015 and 2 mg/kg AM251 were administered through caudal vein. The groups were control, sham, ischemia, vehicle, AM251, JWH-015 and AM251 + JWH-015. Animals were sacrificed at 14 days after reperfusion. The AM251 + JWH-015 group showed a significant increase in the protein expressions of AKT1, Bad 14-3-3, Bcl-2 and Bcl-XL, but it showed a considerable decrease in the protein expressions of Bad and JNK1/2 (p ≤ 0.05 vs. AM251, and JWH-015 groups). The AM251 + JWH-015 group had a significant higher number of alive cells and lower number of TUNEL-positive cells in the CA1 hippocampal area, and it also had a considerable improvement of spatial memory (p ≤ 0.05 vs. AM251, and JWH-015 groups). The results of this study showed that combined application of AM251 and JWH-015 could be neuroprotective against detrimental effects of ischemia probably via suppression of neuronal apoptosis and maintenance of their survival.