Abstract

Since the role of excitatory amino acids such as glutamate and aspartate and their receptors mediating cellular injury through various mechanisms were known in hypoxic-ischemic injury and associated diseases of central nervous system, blocking agents for transmitter release or receptors have been tried to reduce the cellular damages and subsequent sequelae experimentally. Several in vitro studies suggested two kinds of glutamate neurotoxicity: (1) rapid toxicity due to influx of sodium or chloride with resultant cellular edema and consequent damage, which is associated with N-methyl-D-Aspartate(NMDA) as well as non-NMDA receptors, (2) calcium mediated delayed toxicity associated mainly with NMDA receptor. This study was conducted to investigate the role of rapid toxicity in hypoxic-ischemic injury. Early lesions of 30 minutes to 24 hours after hypoxic-ischemic insult were examined by autoradiography with radiolabelled glutamate and kainitic acid (KA) as well as light and electron microscopy. Late changes were evaluated on formaldehyde-acetic acid-methanol(FAM) fixed brain 1 week after the insult. Cornus ammonis(CA) l of hippocampus showed the highest density of NMDA receptors, which was decreased constantly from 2 hours to 24 hours. In contrast, CA3 of hippocampus showed the highest density of KA receptors, which was the lowest at 6 hour and increased thereafter. Light microscopic examination showed the worst changes during 30 minutes to 6 hours. After 1 week, most of the cases showed degeneration of neurons and CAI and CA3 did not show the difference. Electron microscopic examination showed marked degenerative changes of neurons as well as neuropils starting from 30 minutes after the insult. In conclusion, rapid toxicity mediated by non-NMDA(KA) receptor seen in CA3 lead to permanent damage in 1 week old lesion.

• Keywords: Hypoxic-ischemic injury;Excitatory amino acid receptor;