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

摘要

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 (MgSO 4) 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 MgSO 4 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 MgSO 4 solution significantly increased the number of surviving neurons and decreased the number of dead neurons. In the intra-cerebral infusion experiment, 1 mmol/l MgSO 4 and 10 mmol/l MgSO 4 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 MgSO 4 solution can provide neuroprotection against DND without changing the CBF and metabolism.