Vink Robert, Cook Naomi L, van den Heuvel Corinna
Discipline of Pathology, School of Medical Sciences, University of Adelaide, Australia.
Magnes Res. 2009 Sep;22(3):158S-162S.
While brain free magnesium levels have been shown to decline in a number of acute and chronic brain pathologies, the mechanisms of such decline and the potential for magnesium administration as a therapeutic intervention are still unclear. In acute brain injury, magnesium therapy has failed in recent clinical trials of trauma, presumably because of an intact blood brain barrier at the time of administration reducing central penetration. Under such conditions, magnesium's peripheral effects on cardiovascular parameters may dominate over the central, and potentially neuroprotective, effects of the compound. In contrast, magnesium has been demonstrated to be beneficial in lacunar strokes, albeit that recent animal studies indicate that this effect is without any significant reduction of lesion size. Postnatal magnesium has also been shown to improve neurological outcome in term neonates with perinatal asphyxia, although this may be limited to cases of mild to moderate brain injury; no effect is observed following severe brain injury. Prenatal magnesium has been reported to be beneficial for outcome in very preterm infants, although this may only be at low doses. Combination therapies are also showing promise in experimental studies, with combined magnesium and mild hypothermia as well as magnesium and polyethylene glycol proving effective in ischemic stroke and in spinal cord injury, respectively. With respect to chronic brain injury, recent results indicate that magnesium deficient mice are susceptible to developing Parkinson's disease, which is consistent with earlier findings that magnesium deficiency over a number of generations is associated with the development of Parkinson's disease. The latter was associated with the appearance of variants of the TRPM channels. Our recent studies have shown that Parkinson's disease is associated with reduced TRPM2 and TRPM7 channel mRNA expression. Taken together, a more complete picture is emerging of the role of magnesium in brain injury, its therapeutic potential as well the mechanisms associated with its decline.
虽然在多种急性和慢性脑部病变中，已显示脑游离镁水平会下降，但这种下降的机制以及镁作为治疗干预措施的潜力仍不清楚。在急性脑损伤中，镁疗法在近期的创伤临床试验中失败了，大概是因为给药时血脑屏障完整，减少了药物向中枢的渗透。在这种情况下，镁对心血管参数的外周作用可能会超过该化合物的中枢作用以及潜在的神经保护作用。相比之下，镁已被证明对腔隙性中风有益，尽管最近的动物研究表明这种作用并没有显著减小病变大小。产后镁也已被证明可改善足月围产期窒息新生儿的神经学预后，尽管这可能仅限于轻度至中度脑损伤的病例；严重脑损伤后未观察到效果。据报道，产前镁对极早产儿的预后有益，尽管这可能仅在低剂量时有效。联合疗法在实验研究中也显示出前景，镁与轻度低温以及镁与聚乙二醇联合分别在缺血性中风和脊髓损伤中被证明有效。关于慢性脑损伤，最近的结果表明，缺镁小鼠易患帕金森病，这与早期的研究结果一致，即多代缺镁与帕金森病的发生有关。后者与TRPM通道变体的出现有关。我们最近的研究表明，帕金森病与TRPM2和TRPM7通道mRNA表达降低有关。综上所述，镁在脑损伤中的作用、其治疗潜力以及与其下降相关的机制正逐渐呈现出更完整的图景。
