IMMUNOHISTOCHEMICAL MARKERS FOR NEURONS AND ASTROCYTES SHOW PAN-NECROSIS FOLLOWING INFUSION OF HIGH-DOSE NMDA INTO RAT CORTEX

This study pertains to the transition between selective neuronal necro sis and the development of cerebral infarction (pan-necrosis). We infu sed the neuron selective excitotoxin N-methyl-D-aspartate (NMDA) at a relatively high concentration (10 mu l of 50 mM NMDA in phosphate buff er, pH 7.4) into the rat cortex. Local injection of lactic acid and a minor stab wound in the cortex were used as a reference. The tissue da mage was evaluated with immunohistochemical markers for neurons (MAP2, parvalbumin) and for astrocytes (GFAP and S100 protein). The stab wou nd and infusion of lactic acid led to a small distinct area of pan-nec rosis with a sharp border to the surrounding tissue. The NMDA lesions were characterized by a center of pan-necrosis with loss of all tissue elements that were larger and less distinctly demarcated than the oth er lesions. This study shows that activation of NMDA receptors per se can induce pan-necrosis, and we conclude that the transition from sele ctive neuronal necrosis to infarction depends on the intensity of the neuronal damage process. (C) 1994 Academic Press, Inc.