Department of Neurosurgery, Juntendo University, Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan.
Brain Res. 2012 Oct 22;1480:72-80. doi: 10.1016/j.brainres.2012.07.039. Epub 2012 Jul 24.
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 [(14)C]iodoantipyrine and [(14)C]deoxyglucose, respectively, on day 5 after the start of either cisternal or intra-cerebral infusion. In the cisternal infusion experiment, 100 mmol/lMgSO(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/lMgSO(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.
几种神经保护策略，如巴比妥酸盐昏迷和低温治疗，在实验研究中很有前景，但在临床试验中疗效有限。镁离子作为一种天然的钙通道阻滞剂，具有血管扩张和神经保护作用。本研究评估了脑池内和脑室内输注硫酸镁（MgSO4）溶液对 CA1 海马锥体神经元迟发性神经元死亡（DND）的神经保护作用，并研究了脑血流（CBF）和代谢变化的参与情况。在第 1 天，将装有不同浓度 MgSO4 溶液的渗透泵植入 Sprague Dawley 大鼠背部，然后开始脑池内或脑室内（左侧 CA1）输注。在第 3 天诱导 10 分钟的全脑缺血，在第 7 天通过苏木精-伊红和 Fluoro-Jade B 染色分别评估 CA1 区存活神经元和死亡神经元的数量。在开始脑池内或脑室内输注后的第 5 天，通过放射性自显影方法使用 [(14)C]碘安替比林和 [(14)C]脱氧葡萄糖分别测定局部 CBF 和葡萄糖利用率（CMRglc）。在脑池内输注实验中，100mmol/L MgSO4 溶液显著增加了存活神经元的数量，减少了死亡神经元的数量。在脑室内输注实验中，1mmol/L 和 10mmol/L MgSO4 溶液以剂量依赖性方式显著增加了输注侧存活神经元的数量，减少了死亡神经元的数量。在海马 CA1 区，局部 CBF 或 CMRglc 均无明显变化。脑池内或脑室内预先给予 MgSO4 溶液输注均可提供对 DND 的神经保护作用，而不改变 CBF 和代谢。
