Neuroprotective Effects of Magnesium Sulfate and Dextromethorphan on Cerebral Ischemia after Middle Cerebral Artery Occlusion in Rats

ABSTRACT

OBJECTIVE: Much evidence implicates that excitatory amino acids play a crucial role in neuronal death under ischemic conditions, of which the neurotoxic effects are thought to be mediated by overstimulation of glutamate receptors causing a massive influx of calcium ions into the cell. The author examined the effect of MgSO4 and dextromethorphan, N-methyl-D-aspartate(NMDA) receptor antagonists, on ischemic injury in a reversible model of middle cerebral artery(MCA) occlusion in rats. MATERIALS AND METHODS: Forty Sprague-Dawley rats were equally divided into four groups and treated with vehicle(group I), MgSO4 in the amount of 90mg/kg(group II), dextromethorphan of 50mg/kg(group III), and simultaneously MgSO4 of 90mg/kg and dextromethorphan of 50mg/kg(group IV). Following the pretreatment, the animals were subjected to 90 minutes of temporary middle cerebral artery occlusion induced by means of a 3-0 poly-L-lysine coated nylon suture inserted retrogradely via the external carotid artery into the internal carotid artery and MCA. Reperfusion was achieved by retracting the occluding suture. RESULTS: Automated, volumetric measurements of the infarct size demonstrated a statistically significant decrease in GroupII, III, IV compared with GroupI. Neuroprotection was greater in Group IV(64.3% reduction in infarct volume, p<0.001, Student's t-test)than that of Group II or Group III(55.0%, p<0.001, 22.9% reduction, p<0.01, respectively). Group II showed a 41.6% reduction in infarct volume compared with Group III(p<0.001), and Group IV showed a 53.7% reduction in infarct volume compared with Group III(p<0.001). Only Group IV demonstrated protection of both cortex and striatum(p<0.001). CONCLUSION: This beneficial effect of MgSO4 and dextromethorphan in transient focal cerebral ischemia, particularly their combined synergistic effect, indicates their possible usefulness in treating patients with acute ischemic stroke.