Cell biological study of glutamate receptor and gap jujunction in delyed neuronal death

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1) Certification of GluR2 hypothesis by antisense GluR210nM, 5μl GluR2 antisense oligonucleatide (ODN) was injected into the rat ventricle 4 times by 12hs interval. At 2 days after the last injection, partial cell loss of pyramidal layer of hippocampal CA1 and CA3 could be seen. GluR2 mRNA and protein were reduced prior to the cell loss. CNQX and Naspm could save the cell damage, but AP5 had no effect on neuronal death by GluR2 antisense. GluR2 antisense also accelerate the damage of CA1 pyramidal cells by sublethal (2min) global ishcemia. These findings strongly suggest the GluR2 hypothesis in the field of delayed neuronal death.2) Development of new AMPA receptor antagonists and the determination of therapeutic window of global ischemiaVarious concentration of Naphtyl acetyl spermine (Naspm) was intraventricularly injected at the time of 0,6,24hs after the bilateral common carotid occlusion in gerbil. Only 10mM Naspm injcted at 0 and 6hs afford neueo protection of CA1 pyramidal cells on 7days after the global ischemia. These results suggest that early application of AMPA antagonists are needed for neuroprotection.3) Roles of gap junction in cerebral ischemiaWe examined the changes in connexin 32,36 and 43 mRNA and protein after global ischemia by in situ hybridization and quantitative Western blotting in C57BL/6 mice, which is the backgroud strain of connexin 32 knockout mouse. All of the mRNA and protein of each connexin were the same lavel of slightly increased after global ischemia. Connexin 32 knockout mice showed increased susceptibility to 10min global ischemia compared to the wild type mice. These findings suggest the neuroprotective role of gap junction to the ischemic damage.