Research ReportNeuroprotective effects of magnesium-sulfate on ischemic injury mediated by modulating the release of glutamate and reduced of hyperreperfusion

This study examined the neuroprotective effects of magnesium-sulfate (MgSO4) on the cerebral blood flow (CBF) and extracellular glutamate concentration in an eleven vessel occlusion (11VO) rat model. Twenty-one male Sprague-Dawley rats (250-350 g) were used for the 11VO ischemic model, which was induced by a 10-min transient occlusion. The animals were divided into 3 groups, including ischemic-induced animals (ischemia group), ischemic-induced and MgSO4 treated animals (MgSO4 group), and sham animals for comparison. The real-time extracellular glutamate concentration was measured using a microdialysis biosensor, and the CBF was monitored by laser Doppler flowmetry. Neuronal cell death in the hippocampal region was observed 72 h after ischemia by several stains (Nissl, DAPI, NeuN, and cleaved caspase3). A significant decrease in %CBF was observed in both the ischemia and MgSO4 groups, such as ~ 10% during the ischemic period. However, the MgSO4 group showed a significant decrease in the initial reperfusion %CBF compared to the ischemia group. A significantly lower level of glutamate release was observed in the MgSO4 group than in the ischemia group during the ischemic and reperfusion episode. Our staining results revealed a significant decrease in neuronal cell death in the hippocampus in the MgSO4 group compared to the ischemia group. These results suggest that MgSO4 is responsible for the protection of neuronal cells by suppressing the release of extracellular glutamate under ischemic conditions and the CBF response during the initial reperfusion period.

Research Highlights► A decrease in the %CBF was observed during the ischemic period in 11VO ischemia rat model, with a consistent increase in glutamate release. ► MgSO4 reduced CBF and release of glutamate during reperfusion period. ► The suppression of the extracellular glutamate levels and sudden increase in CBF during the initial reperfusion period by MgSO4 may have neuroprotective effects on neuronal cells in an 11VO model.