329회 The Delayed Neuronal Death in Transient Cerebral Ischemia: Free R…

329회

연사 : 원 무 호 , 한림대학교 의과대학

제목:  The Delayed Neuronal Death in Transient Cerebral Ischemia: Free Radical Damage or Excitotoxicity?

Abstract

Ischemic injury to neurons is primarily due to the interruption of blood flow, lack of oxygenation, and subsequent reoxygenation of the brain (ischemia-reperfusion). There are two hypotheses on the mechanism responsible for neuronal injury in this event. One hypothesis focuses on oxidative damage involving reactive oxygen species, the other on N-methyl-D-aspartate receptor (NR)-mediated excitotoxicity due to excessive extracellular glutamate concentration. In the present study, we investigated the correlation between both N-methyl-M-aspartate receptor (NR) subunits (NR1 and NR2A/B) and glutamate transporters (EAAC-1, GLT-1 and GLAST) expressions, and oxidative DNA damage marker, 8-hydroxy-2’-deoxyguanosine (8-OHdG), in the series of events that link brain ischemia to neuronal death using a gerbil model in vivo. As the results, at 30 min after ischemia-reperfusion, the intensities of NR, GLT-1, GLAST and 8-OHdG immunoreactivities were markedly increased in CA1 area. In contrast, EAAC-1 immunoreactivity was declined in the CA1 at 30% of the sham level. From 3 hr after ischemia, the densities of NR1 and GLAST immunoreactivity were significantly decreased in the CA1, however NR2A/B, GLT-1, EAAC-1 and 8-OHdG immunoreactivities were enhanced in the CA1 area until 12 hr after ischemia. At 24 hr, NR2A/B and all glutamate transporters immunoreactivities were saliently decreased whereas 8-OHdG immunoreactivity preserved in the CA1 area. These results suggest that oxidative stress and the excitotoxicity in the CA1 area may simultaneously trigger neuronal damages at early time after ischemia. In addition, the augmentation of free radical damage in this area may eventually precede the delayed neuronal death via both oxidative DNA damage and changes in functionality of glutamate transporters.