Elucidation of the mechanism of action of novel antiepileptic drugs using functionalized magnetic nanoparticles and exploration of their neuroprotective effects
| Project/Area Number |
16K10000
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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 | Tokyo Medical University |
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Principal Investigator |
Yamanaka Gaku 東京医科大学, 医学部, 准教授 (70349512)
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| Co-Investigator(Kenkyū-buntansha) |
石 龍徳 東京医科大学, 医学部, 主任教授 (20175417)
河島 尚志 東京医科大学, 医学部, 主任教授 (70224772)
半田 宏 東京医科大学, 医学部, 特任教授 (80107432)
善本 隆之 東京医科大学, 医学部, 教授 (80202406)
松本 哲哉 東京医科大学, 医学部, 兼任教授 (10256688)
出雲 信夫 横浜薬科大学, 薬学部, 教授 (70368976)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | サイトカイン / 急性脳症 / てんかん / 新規抗てんかん薬 / アポトーシス / 炎症 / 機能性ナノ磁気微粒子 / モデルマウス / 脳保護 / フローサイトメトリー / 脳症 |
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| Outline of Final Research Achievements |
The pathogenesis of acute encephalopathy and epilepsy is still unclear and new treatments are desired. We identified a candidate protein for levetiracetam (LEV) using functional nanomagnetic particles. In a mouse model of encephalopathy, we observed a tendency to decrease IL-1β and IL-6 mRNA in the cerebral cortex after administration of LEV. However, there was no evident difference between the effects of diazepam and those of LEV, and the mechanism of action of LEV could not be elucidated. Cerebrospinal fluid levels of Granzyme A and pro-inflammatory cytokines were significantly higher in the Infection-associated acute encephalopathy than in the control group. In refractory epilepsy patients, intracellular cytokines (monocytes;IL-1β,TNF-α、CD8T cells;IL-17 and NK cells; IFN-γ) were significantly higher compare to the control group. These results suggest the intervention of immunological mechanisms in the pathogenesis of acute encephalopathy and epilepsy.
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| Academic Significance and Societal Importance of the Research Achievements |
脳症モデルマウスの検討にて、LEVによる炎症性サイトカインの低下が大脳皮質のmRNAレベルで確認され、抗てんかん薬による免疫学的機序の関与が示唆された。急性脳症の病態にGranzyme Aを介したアポトーシスの関与、てんかんの病態に血清や髄液だけではなく、細胞内の炎症性サイトカインの上昇が確認された。急性脳症やてんかんの病態に炎症やアポトーシスに伴う免疫学的機序の関与が明らかになれば、新たな治療法に繋がる可能性がある。
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Report
(5 results)
Research Products
(88 results)
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[Presentation] Granzyme A as a potential biomarker of pediatric acute encephalopathy and complex febrile seizures2018
Author(s)
Yamanaka G, Takahashi R, Oana S , Morichi S, Takamatsu T, Ishida Y, Morishita N, Takeshita M, Go S, Kashiwagi Y, Kawashima H
Organizer
The 20th Annual Meeting of International Symposium on Severe Infantile Epilepsies
Related Report
Int'l Joint Research
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[Presentation] Role of granzymes in the pathology of pediatric acute encephalopathy2018
Author(s)
Yamanaka G, Takahashi R, Watanabe Y, Takamatsu T, Takeshita M, Morichi S, Ishida Y, Morishita N, Oana S, Kashiwagi Y, Kawashima H
Organizer
第41回日本神経科学学会
Related Report
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[Presentation] Five cases with epilepsy presenting voltage-gated sodium channel gene mutations2017
Author(s)
Ishida Y, Yamanaka G, Urabe T, Takeshita M, Morishita N, Morichi S, Suzuki S, Ushio M, Oana S, Kato M*, Kawashima H
Organizer
14th Asian and Oceanian Congress of Child Neurology
Related Report
Int'l Joint Research
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[Presentation] 急速に脳浮腫が進行し、予後不良な経過をたどったけいれん重積型(二相性)急性脳症2017
Author(s)
森山 陽子、高梨 潤一, 林 北見, 白戸 由理, 安川 久美, 本田 隆文, 渡邉 誠司, 久保田雅也, 寺嶋 宙, 北村 太郎, 藤田 雄治, 山中 岳
Organizer
第59回日本小児神経学会学術集会
Related Report
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