Refractory mechanisms of intractable epilepsy: an experimental analysis of polymicrogyria and clinical approaches
| Project/Area Number |
15K09617
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | てんかん / 皮質形成異常 / 多小脳回症 / インターニューロン / けいれん準備性 / Epilepsy / Polymicrogyria / Interneuron / GAP43 / 介在神経細胞 |
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| Outline of Final Research Achievements |
Intraperitoneal pentylenetetrazole injection elicited seizures of variable severity in the polymicrogyria rats (PMG). Neuron degeneration and reactive axonal elongation were significantly and widely distributed in the interneurons of PMG, suggesting that the relatively selective vulnerability of inhibitory interneurons constitutes the basis for the decreased seizure threshold observed in this model of polymicrogyria. In the clinical investigations of patients with severe motor and intellectual disabilities (SMID), an electroencephalogram analysis revealed that multifocal spike discharge was more frequently detected in the profound SMID group than in the non-profound SMID group. Multifocal epileptogenesis was thought to be one of the most characteristic findings in SMID patients, which may be closely associated with a factor involved in the intractability of epilepsy in these patients.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、難治性てんかんの動物実験モデルを利用した基礎研究と、高度の脳障害を有するてんかん症例を対象とした臨床研究を相互に関連させ、多面的にてんかんの難治性病態の解明を試みた研究課題である。両者の研究結果の考察から、てんかんの難治性病態には病理学的には介在神経細胞の脆弱性による興奮・抑制機構の不均衡が、電気生理学的には脳の広範囲な領域に分布する多焦点性の発作活動の関与が重要な要因であると推測した。
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Report
(5 results)
Research Products
(13 results)
