PT - JOURNAL ARTICLE AU - Deanne L. Heath AU - Robert Vink TI - Optimization of Magnesium Therapy after Severe Diffuse Axonal Brain Injury in Rats DP - 1999 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1311--1316 VI - 288 IP - 3 4099 - http://jpet.aspetjournals.org/content/288/3/1311.short 4100 - http://jpet.aspetjournals.org/content/288/3/1311.full SO - J Pharmacol Exp Ther1999 Mar 01; 288 AB - 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 μmol/kg and 750 μmol/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. The American Society for Pharmacology and Experimental Therapeutics