Suppression of Spreading Depression of Leão in Neocortex by an N-Methyl-D-Aspartate Receptor Antagonist

Spreading depression has been implicated in the pathophysiology of a number of diseases such as migraine, stroke and epilepsy. The characteristics of this phenomenon were explored in neocortex of anesthetized rats. Spreading depression was produced in 10 of 15 animals using mechanical, electrical and chemical stimulation. Mean amplitude of the DC shift was -9.3 mV, mean duration at any one electrode 65 sec and rate of spread 2-5 mm/min. Spreading depression was facilitated by focal interictal spike activity induced by penicillin and completely blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-aminophosphonovaleric acid (APV), providing further evidence that excitatory amino acid neurotransmission is a critical element in the development or propagation of the phenomenon.