Cyanocobalamin improves memory impairment via inhibition of necrosis and apoptosis of hippocampal cell death after transient global ischemia/reperfusion

Document Type : Original Article


1 School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

2 Neurosciences Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

3 Neurobiomedical Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Department of Sport Sciences, Ilam University, Ilam, Iran

5 Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran


Objective(s): Brain ischemia/reperfusion (I/R) causes irreversible damage, particularly in the hippocampus. Cyanocobalamin (CNCbl) is known to be crucial for the proper operation of the nervous system. Vitamin B12 has been demonstrated to exert antioxidant effects via direct and indirect mechanisms. It can also protect cortical neurons against glutamate cytotoxicity. This research was conducted to examine CNCbl protection against neuronal cell death in the rat hippocampal region following transient cerebral ischemia.
Materials and Methods: In this experiment, 48 male Wistar rats were selected, which were randomly divided into four groups (n=12 in each group): sham, ischemia/reperfusion, ischemia/reperfusion + CNCbl 200 and 400 (µg/kg). By occlusion of both common carotids, ischemia induction was performed within 20 min. CNCbl at the doses of 200 and 400 µg/kg was injected (IP) at the start of the reperfusion, 24 and 48 hr following reperfusion. The spatial memory was assessed 7 days following ischemia through the Morris water maze test. Antioxidant enzymes, apoptosis, and necrosis were measured after behavioral tests.
Results: CNCbl significantly improved spatial memory impairments (p <0.05), also CNCbl therapy significantly increased both glutathione (p <0.01) and superoxide dismutase (p <0.05) and reduced malondialdehyde (p <0.01) and TNF-α (p <0.05) in comparison with the ischemia group. In addition, CNCbl significantly decreased both apoptosis and necrosis in the hippocampus CA1 (p <0.01).
Conclusion: CNCbl improves memory impairment following ischemia injury by decreasing neuronal cell death via its antioxidant properties.


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