| Project/Area Number |
10671321
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Juntendo University |
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Principal Investigator |
KUSUMOTO Masayuki Juntendo University, Dep.of Medicine, Assistant Neurosurgeon, 医学部, 助手 (20195449)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Kentaro Juntendo University, Dep.of Medicine, Associate Professor, 医学部, 助教授 (30200364)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Hypothermia / Neuron / Glutamate / Iodoacetate |
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| Research Abstract |
To elucidate the mechanism of the neuronal protection against ischemia by brain hypothermia, we studied the effect of low temperature on glutamate-induced or iodoacetate (IAA)-induced injury in primary hippocampal neuronal cultures of rat in vitro.
1. Glutamate neurotoxicity
To examine the effect of hypothermia on glutamate neurotoxicity, the cultivated, medium was maintained at 37℃ or 30℃ during 15 min of glutamate treatment. Survival neurons were counted 24 h after glutamate treatment. Marked neuronal injury was produced 24 h after 15 min of 100 μM glutamate treatment under the condition of both 37℃ and 30℃.These results indicate that brain hypothermia cannot save neurons once glutamate is released during ischemia, and that intraischemic hypothermia in vivo prevents the development of ischemic neuronal injury probably by suppressing extracellular glutamate release.
2. IAA neurotoxicity
1) To examine the effect of hypothermia on IAA neurotoxicity, the cultivated medium was maintained at 37℃ or 30℃ during the beginning 30 min after 5 min IAA treatment. Marked neuronal injury was produced 24 hours after 5 min of 1mM IAA treatment under the condition of 37℃. In contrast, when the temperature was maintained at 30℃ during the beginning 30 min after IAA treatment, most of neurons survived 24 hours after histotoxic hypoxia.
2) Cultivated neurons were incubated with 5μM dichlorofluorescein diacetate (DCFH-DA) for 5 min at 3 h after 5 min of 1 mM IAA treatment. DCF, which is a fluorescent molecule, was detected by now cytometry. DCF fluorescence of 30℃-treated group decreased as compared with 37℃-treated one.
These results indicate that hypothermia, even if which starts at the end of IAA treatment, protects neurons against o4dative stress mediated IAA neurotoxicity.
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