J Korean Neurosurg Soc.  1999 Oct;28(10):1389-1397.

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

• Mok JH
• Kwon JT
• Lee YB
• Kim YB
• Min BK
• Hwang SN
• Choi DY
• Suk JS

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.

Keyword

Cerebral ischemia; Magnesium sulfate; Dextromethorphan; Neuroprotection; Rats

MeSH Terms

Animals
Brain Ischemia*
Calcium
Carotid Artery, External
Carotid Artery, Internal
Dextromethorphan*
Excitatory Amino Acids
Humans
Infarction, Middle Cerebral Artery*
Ions
Magnesium Sulfate*
Magnesium*
Middle Cerebral Artery*
Neurons
Neuroprotective Agents*
Nylons
Rats
Rats, Sprague-Dawley
Receptors, Glutamate
Reperfusion
Stroke
Sutures
Calcium
Dextromethorphan
Excitatory Amino Acids
Ions
Magnesium
Magnesium Sulfate
Neuroprotective Agents
Nylons
Receptors, Glutamate