ABSTRACT
We examined whether creatine administration could exert neuroprotective effects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid. Oral administration of 1% creatine significantly attenuated striatal excitotoxic lesions produced by NMDA, but had no effect on lesions produced by AMPA or kainic acid. Both creatine and nicotinamide can exert significant protective effects against malonate-induced striatal lesions. We, therefore, examined whether nicotinamide could exert additive neuroprotective effects with creatine against malonate-induced lesions. Nicotinamide with creatine produced significantly better neuroprotection than creatine alone against malonate-induced lesions. Creatine can, therefore, produce significant neuroprotective effects against NMDA mediated excitotoxic lesions in vivo and the combination of nicotinamide with creatine exerts additive neuroprotective effects.
Subject(s)
Creatine/therapeutic use , Excitatory Amino Acid Agonists/toxicity , Excitatory Amino Acid Antagonists/therapeutic use , Kainic Acid/toxicity , Malonates/toxicity , N-Methylaspartate/toxicity , Neuroprotective Agents/therapeutic use , Niacinamide/therapeutic use , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/toxicity , Administration, Oral , Animals , Calcium/metabolism , Corpus Striatum/drug effects , Corpus Striatum/pathology , Creatine/administration & dosage , Creatine/pharmacology , Energy Metabolism/drug effects , Excitatory Amino Acid Antagonists/administration & dosage , Excitatory Amino Acid Antagonists/pharmacology , Male , Mitochondria/drug effects , Mitochondria/metabolism , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/pharmacology , Niacinamide/administration & dosage , Niacinamide/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
When injected into the rat striatum, quinolinic acid causes dose-dependent widespread cell death. All cell types, including the NADPH-diaphorase-positive neurons appear to be sensitive to the toxin. The latter cells are destroyed by quinolinic acid injections of 180 nmol per striatum, this effect being blocked by the concomitant administration of 5 mg/kg of the non-competitive N-methyl-D-aspartate antagonist MK-801. We report that guanosine-5'-monophosphate (GMP), at a dose of 360 nmol, is equally effective in protecting the diaphorase-positive cells against quinolinate toxicity.
