| Project/Area Number |
61440063
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Okayama University |
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Principal Investigator |
MORI Akitane Okayama Univ. Med. Sch., Professor, 医学部, 教授 (20028434)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUKAWA Kiminao Okayama Univ. Med. Sch., Instructor, 医学部, 講師 (40137154)
NISHIMOTO Akira Okayama Univ. Med. Sch., Professor, 医学部, 教授 (50032850)
WATANABE Yoko Okayama Univ. Med. Sch., Assistant, 医学部, 助手 (70135945)
HIRAMATSU Midori Okayama Univ. Med. Sch., Assistant, 医学部, 助手 (70124790)
YOKOI Isao Okayama Univ. Med. Sch., Assistant, 医学部, 助手 (80150366)
中村 成夫 岡山大学, 医学部, 助教授 (50164299)
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| Project Period (FY) |
1986 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | post-traumatic epilepsy / iron-induced epileptogenic focus / superoxide anion / hydroxyl radical / superoxide dismutase / lipideperoxide / epigallocatechin / EPC / 鉄塩誘導 / ヒドロキシル・ラジカル / クエン酸鉄 / ス-パ-オキシドジスムタ-ゼ / アスコルビン酸ラジカル / 鉄塩誘導実験てんかんモデル / ヒドロキシル・ラジカル、アスパラギン酸放出 / スーパオキシド・ジスムターゼ / EPC-K_1 / 酸素ストレス / C-fOS蛋白 / 鉄イオン / 活性酸素ラジカル / スーパーオキシドジスムターゼ / カテコールアミン / セロトニン / グアニジノ酢酸 / メチルグアニジン / ヒドロキシル・ラジカル(・OH) / 【Na^+】,【K^+】-ATPase / 【Mg^(2+)】-ATPase / マロンジアルデヒド / ドーパミン / ノルエピネフリン / 外傷性てんかんモデル |
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| Research Abstract |
We studied on pathogenesis of post-traumatic epilepsy using iron- induced epileptic rats as an experimental post-traumatic epilepsy, and also on rational treatments for it, being based on these experimental results. Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Biological iron is normally protein bound in hemoglobin and transferrin. We observed that iron liberated from hemoglobin is associated with generation of active oxygen species, such as O^-_ and .OH. Moreover, we demonstrated that hemoglobin itself promotes oxygen free radical generation.
Then we estimated accelerated production of thiobarbituric acid reactive substances (TBARS), and suggested that oxygen free radicals, especially .OH is responsible for the induction of peroxidation of neuronal lipids, that is an injury of neuronal membranes. On the other hand, we demonstrated that .OH accelerates production of guanidino compounds in the brain, such as methylguanidine and guanidinoacetic acid. They are endogenous convulsants in the brain. These reactions may follow by excitatory and inhibitory neurotransmitter disorders, and may lead to development of epileptic discharges in the epileptogenic focus. Then, we found that treatment of epigallocatechin(EGC) or a phosphate diester of vitamins E and C (EPC), which are a potent .OH scavenger and anti-oxidant, significantly inhibited the formation of malondialdehyde and epileptic discharges in the iron induced epileptic focus.
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