Blockade of N-methyl-D-aspartate-sensitive acidic amino acid receptors inhibits ischemia-induced accumulation of purine catabolites in the rat striatum.

The effect of blocking N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid (EAA) receptors during brain ischemia was studied in order to test a link between EAAs and neuronal energy metabolism. The receptors were blocked unilaterally in the rat striatum before, during and after an ischemic insult. The receptor blocker, D-2-amino-5-phosphonovalerate (D-APV) was administered by dialysis perfusion, which also allowed continuous sampling for analysis of adenosine triphosphate degradation products, i.e. purine catabolites, in control and D-APV-treated striata. Purine catabolites were analysed with reversed-phase liquid chromatography. Hypoxanthine, xanthine, inosine and adenosine increased dramatically in the striatum during ischemia and reached maximum levels during early reperfusion. D-APV reduced the extracellular accumulation of all measured purine catabolites during ischemia/reflow and improved to some extent the recovery of the striatal electroencephalographic activity in the majority of the animals. The results suggest that NMDA receptor blockade attenuates acute changes in energy metabolism during ischemia.