Protective effect of memantin induced by cerebral ischemia and reperfusion injury in rats

Stroke is the third leading cause of death after coronary heart disease and cancers. Ischemic stroke is the most common type of stroke.The severity of apoptosis developing after hypoxia-ischemia and reperfusion is an indicator of cerebral injury. In cerebral ischemia, there are many factors initiating the events progressing to cell death. The most common leading cause is excessive increase in intracellular calcium concentration. Ion channels in N-methyl D-aspartate (NMDA) receptors cause cell death by increasing Ca+2 entries into the cell.Memantine is non-competitive excitatory amino acid blocker binding to phenylcyclidine binding site of NMDA receptor. In vitro and in vivo studies suggesting administration of memantine before and after ischemia decreasing the neural injury have been published. This study was conducted with the hypothesis of memantine molecule could have decreasing effect on neuronal injury resulting in apoptosis especially in penumbra region after ischemia. Experimental study was performed in three groups each of them including 7 rats. No procedure was performed in control group and it was used for evaluation of the normal brain tissue. Transient focal cerebral ischemia was performed by clamping the right common carotid arteries of the rats in ischemia and ischemia-drug groups. Ten mg/kg intraperitoneal memantine was administered in ischemia-drug group 30 minutes after ischemia and for 5 days. All of the rats were sacrificed after the experiment. Antioxidant and oxidant levels of the cerebral tissues were measured. Apoptotic cells were determined by immunohistochemically staining with TUNEL method. When the group administered memantine was compared with ischemia group, it was observed that memantine decreased apoptotic cells in the brain tissue and provided evident improvement in oxidant levels (p<0.05).In conclusion, in this study, we considered that memantine administration could be effective in decreasing neuronal injury occurring in experimental cerebral ischemic tissue.Keywords: Ischemic stroke, Memantine, Rat