Research ReportNovel neuroprotective effect of cisternal and intra-cerebral magnesium sulfate solution infusion on delayed cerebral death in rat hippocampal neurons after transient global ischemia

Several neuroprotective strategies such as barbiturate coma and hypothermic therapies have been promising in experimental studies but had limited efficacies in clinical trials. Magnesium ion has vasodilator and neuroprotective properties as a natural calcium blocker. The neuroprotective effects of cisternal and intra-cerebral infusion of magnesium sulfate (MgSO4) solution were evaluated against delayed neuronal death (DND) of CA1 hippocampal pyramidal neurons, and the involvement of changes in cerebral blood flow (CBF) and metabolism were investigated. Osmotic pumps with various MgSO4 solutions were embedded in the Sprague Dawley rat backs on day 1 and either cisternal or intra-cerebral (left CA1) infusion started. Global ischemic insult for 10 min was induced on day 3, and the numbers of surviving neurons and dead neurons in the CA1 region were evaluated by hematoxylin-eosin and Fluoro-Jade B staining, respectively, on day 7. The regional CBF and glucose utilization rate (CMRglc) were determined by autoradiographic methods using [14C]iodoantipyrine and [14C]deoxyglucose, respectively, on day 5 after the start of either cisternal or intra-cerebral infusion. In the cisternal infusion experiment, 100 mmol/l MgSO4 solution significantly increased the number of surviving neurons and decreased the number of dead neurons. In the intra-cerebral infusion experiment, 1 mmol/l MgSO4 and 10 mmol/l MgSO4 solution significantly increased the number of surviving neurons and decreased the number of dead neurons in the infusion side in dose-dependent manner. Neither regional CBF or CMRglc changed significantly in the CA1 of the hippocampus. Pretreatment with either cisternal or intra-cerebral infusion with MgSO4 solution can provide neuroprotection against DND without changing the CBF and metabolism.

► Neuroprotective effects of MgSO4 solution were evaluated in hippocampal CA1. ► Involvement of changes in CBF and CMRglu was also investigated. ► Neither regional CBF or CMRglu changed significantly in hippocampal CA1. ► Cisternal or intracerebral infusion of MgSO4 solution prevents delayed neuronal death.