|Combined Neuroprotective Action of JWH-015 and AM251 in the CA1 Hippocampal Area of Rat Model of Transient Global Cerebral Ischemia|
|Maryam Shiasi1, Keywan Mortezaee2, Farid Abolhassani1, Zahra Nadia Sharifi3, Marzieh Derakhshan-horeh1,4, Azim Hedayatpour1|
|1Department of Anatomy, School of Medicine, Tehran University of Medical Science, Tehran, Iran
2Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
3Department of Anatomy, School of Medicine, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
4Gynecology and andrology center, khanevadeh-hospital, Esfahan, Iran
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Keywords : Apoptosis,CA1, Survival, Global cerebral ischemia
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Objective: Transient global cerebral ischemia (TGCI) induces by occlusion of bilateral common carotid artery (BCCAO), and it mediates neuronal cell deathof 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 aim of this study was to investigate the role of combined application of JWH-015 with AM251 in the rat model of GCI.
Materials and Methods: Male Wistar rats underwent 20 min of ischemia followed by reperfusion. Then, 1mg/kg JWH-015 and 2 mg/kg AM251were administered through caudal vein.The groups were control, sham, ischemia, vehicle, AM251, JWH-015 and AM251 + JWH-015.Animals were sacrificed 1 weekafter BCCAO.
Results: The AM251 + JWH-015 group indicated a significant increase in the protein expressions of AKT1, Bcl-XL, Bcl-2 and Bad 14-3-3, 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 apoptotic 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).
Conclusion: The results of this study indicated 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.
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