Optimization of magnesium therapy after severe diffuse axonal brain injury in rats

作     者：Heath, DL Vink, R 

作者机构：James Cook Univ N Queensland Dept Physiol & Pharmacol Townsville Qld 4811 Australia 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第288卷第3期

页      面：1311-1316页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

主　　题：脑/代谢 脑损伤/药物疗法 脑损伤/代谢 剂量效应关系 药物 氯化镁/治疗应用 镁化合物/代谢 镁化合物/治疗应用 硫酸镁/治疗应用 磁共振波谱学 神经病学检查 神经保护药/治疗应用 大鼠 Sprague-Dawley 时间因素 动物 男(雄)性 大鼠 

摘      要：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 mu mol/kg and 750 mu mol/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.