Neuroscience and Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor.
We evaluated the neuroprotective effects of systemically administered magnesium against N-methyl-D-aspartate (NMDA)-mediated brain injury in perinatal rats. Postnatal day (PND) 7 rats received unilateral intrastriatal injections of 25 nmol NMDA followed 15 min later by single or multiple doses of magnesium intraperitoneally (i.p.). Animals were sacrificed five days later and the severity of brain injury was assessed by comparison of the weights of the injected and contralateral cerebral hemispheres. NMDA injection reduced the weight of the injected cerebral hemisphere by 31 +/- 3%. Single doses of magnesium reduced the severity of NMDA-induced brain injury in a dose-dependent fashion (2 mmol/kg, 29 +/- 11% protection; 3 mmol/kg, 52 +/- 12% protection; 4 mmol/kg, 62 +/- 7% protection). Multiple doses of magnesium reduced brain injury by 65 +/- 4%. These data demonstrate that systemically administered magnesium antagonizes the neurotoxic effects of NMDA in vivo in perinatal rats.