Mg2+ antagonizes alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced brain damage and convulsions

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), an agonist of the non-N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, was used to imitate glutamate-induced brain injury. A single intracerebroventricular injection of AMPA (9 nmol; 1.7 micrograms) induced convulsive reactions and heavy neurodegeneration in the hippocampal formation. MgSO4 (600 mg/kg), administered 20 min prior to or simultaneously with AMPA exposure, was able to protect completely against this non-NMDA-induced neurotoxicity. Magnesium is suggested to be a hopeful therapeutic principle for glutamate-mediated brain disorders.