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 necrosis and the development of cerebral infarction (pan-necrosis). We infused the neuron selective excitotoxin N-methyl-D-aspartate (NMDA) at a relatively high concentration (10 microliters of 50 mM NMDA in phosphate buffer, 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 damage was evaluated with immunohistochemical markers for neurons (MAP2, parvalbumin) and for astrocytes (GFAP and S100 protein). The stab wound and infusion of lactic acid led to a small distinct area of pan-necrosis 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 other lesions. This study shows that activation of NMDA receptors per se can induce pan-necrosis, and we conclude that the transition from selective neuronal necrosis to infarction depends on the intensity of the neuronal damage process.
Ingvar
M
M
Department of Clinical Neuroscience, Karolinska Institute and Hospital, Stockholm, Sweden.
Schmidt-Kastner
R
R
Meller
D
D
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D002540:Cerebral Cortex / Q000187:drug effects* / Q000293:injuries / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007267:Injections; D007773:Lactates / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage* / Q000494:pharmacology; D009336:Necrosis; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D014951:Wounds, Stab / Q000503:physiopathology
D015415:Biomarkers; D007773:Lactates; D016202:N-Methylaspartate