Non-NMDA mechanism in the inhibition of cellular apoptosis and memory impairment induced by repeated ischemia in rats

Katsunori Iwasaki, Eun Hee Chung, Nobuaki Egashira, Izzettin Hatip-Al-Khatib, Kenichi Mishima, Takashi Egawa, Keiichi Irie, Michihiro Fujiwara

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The spatial memory impairment and expression of apoptotic cells in hippocampal CA1 cells were investigated in rats using single and repeated ischemia models. The neuroprotective and memory-improving effect of YM-90K, an α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, was compared to MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. Twice-repeated ischemia, but not single ischemia, impaired the spatial memory and increased expression of apoptotic cells. YM-90K, given before and 6 h after the second reperfusion, significantly improved the memory and reduced the apoptotic cells 7 days after the second reperfusion in repeated ischemia. MK-801 neither improved the spatial memory nor reduced apoptotic cells. The present study showed that delayed expression of apoptotic cells is mediated by mechanisms involving AMPA receptors, but not by NMDA receptor, during the late phase after reperfusion. YM-90K could provide neuroprotective activity and improve the spatial memory impaired by repeated ischemia.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalBrain Research
Issue number1
Publication statusPublished - Jan 2 2004
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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