Heath D L, Vink R
Department of Physiology and Pharmacology, James Cook University, Townsville, Queensland, Australia.
J Pharmacol Exp Ther. 1999 Mar;288(3):1311-6.
A number of studies have demonstrated that magnesium salts given after traumatic brain injury improve subsequent neurologic outcome. However, given that these earlier studies have used a number of different salts, dosages, and routes of administration, follow-up studies of the neuroprotective properties of magnesium are complicated, with comparisons to the earlier literature virtually impossible. The present study has therefore characterized the dose-response characteristics of the most commonly used sulfate and chloride salts of magnesium in a severe model of diffuse traumatic axonal injury in rats. Both magnesium salts improved neurologic outcome in rats when administered as a bolus at 30 min after injury. The i.v. and i.m. optima of each salt was 250 micromol/kg and 750 micromol/kg, respectively. The identical concentrations required for improved neurologic outcome suggest that improvement in outcome was dependent on the magnesium cation and not the associated anion. Subsequent magnetic resonance studies demonstrated that the administered magnesium penetrated the blood-brain barrier after injury and resulted in an increased brain intracellular free magnesium concentration and associated bioenergetic state as reflected in the cytosolic phosphorylation potential. Both of these metabolic parameters positively correlated with resultant neurologic outcome measured daily in the same animals immediately before the magnetic resonance determinations.
多项研究表明，创伤性脑损伤后给予镁盐可改善后续神经功能转归。然而，鉴于这些早期研究使用了多种不同的盐类、剂量和给药途径，镁神经保护特性的后续研究变得复杂，几乎无法与早期文献进行比较。因此，本研究在大鼠弥漫性创伤性轴索损伤的严重模型中，对最常用的硫酸镁和氯化镁盐的剂量反应特性进行了表征。两种镁盐在损伤后30分钟以推注方式给药时，均可改善大鼠的神经功能转归。每种盐的静脉注射和肌肉注射最佳剂量分别为250微摩尔/千克和750微摩尔/千克。改善神经功能转归所需的相同浓度表明，转归的改善取决于镁阳离子而非相关阴离子。随后的磁共振研究表明，给药后的镁在损伤后穿透血脑屏障，导致脑内细胞内游离镁浓度增加以及相关生物能状态增加，这在胞质磷酸化电位中有所体现。这两个代谢参数均与在磁共振测定前立即对同一动物每日测量的神经功能转归呈正相关。
