| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
We investigated a pathogenetic role for expression in interleukin-1β converting enzyme (ICE) and interleukin-1β (IL-1β) in ischemic tolerance phenomenon. Male Mongolian gerbils were subjected to 5 min forebrain ischemia with or without 2 min sublethal ischemia 24 hours before the 5 min lethal ischemia. Animals were transcardially perfused using 4% paraformaldehyde at 1, 2, 3, 4, or 7 days after the lethal iuschemia, and paraffin-embedded coronal sections including hippocampus were cut on a microtome. Sections were stained with hematoxylin and eosin (HE) staining, and studied immunohistochemically using anti-serum against ICE or IL-1β. Furthermore TUNEL method was applied to the sections to evaluate neuronal DNA fragmentation in the hippocampal CA1 subfield. In the HE stained sections, marked reduction in number of hippocampal neurons was observed from 4 days after lethal ischemia, but the neuronal death was significantly suppressed by preconditioning. ICE immunoreactive neurons were observed from 2 to 4 days after lethal ischemia, although such neurons were scattered form 3 to 4 days in the preconditioned animals. IL-1β was strongly expressed from 4 days, but occasionally scattered in the preconditioned animals. Most of the IL-1β positive cells were microglia. TUNEL positive neurons were markedly increased from 3 days, although less observed in the preconditined animals. These suggest a role for apoptotic suppressive mechanisms in ischemic tolerance phenomenon.
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