| Project/Area Number |
17K08356
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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 |
Natural medicines
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
Kouichi itoh 徳島文理大学, 薬学部, 教授 (30291149)
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| Co-Investigator(Kenkyū-buntansha) |
石原 康宏 広島大学, 統合生命科学研究科(総), 准教授 (80435073)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | てんかん / 五苓散 / 脳波 / 脳内炎症 / 血液脳関門 / 脳浮腫 / 漢方薬 / MRI / 重積発作 / サイトカイン / ミクログリア / FACS / 疾患モデル |
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| Outline of Final Research Achievements |
GOREI-SAN (GRS) has been used for water intoxication. Recently there have been a lot of clinical application studies of GRS
GRS was orally administered 3 times a day (100 mg/kg) after status epilepticus (SE), and in the early stage (2 to 3 days), it suppressed AQP4-mediated transient BBB permeability and vasogenic edema in the hippocampus. In addition, it was observed that the marker of cerebral inflammation Pentraxin3 was markedly increased. Microglia and infiltrating macrophages in the brain were activated, and many proinflammatory cytokines were also highly expressed. This was called SE-induced brain cytokine storm. GRS regulated this cytokine storm. However, long-term EEG measurements did not show a significant effect of suppressing the appearance of epileptiform discharges by GRS. Therefore, the administration of GRS alone limited the effect of suppressing seizures, while suppressing the inflammation-related reaction in the brain.
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| Academic Significance and Societal Importance of the Research Achievements |
世界的な高齢社会を迎え、脳卒中、アルツハイマー病など脳器質性病変を原因とする２次性てんかん発症率が上昇し続けている。てんかん発作は、日常生活に大変な不安をもたらしQOL低下を招く。従って、てんかん発症予防は大変重要な課題であり漢方療法も有用である。てんかん発症における脳内水代謝異常と炎症に関わる方剤、五苓散を用いて検討した。てんかん発症初期段階における脳浮腫、脳内炎症を五苓散は顕著に抑制した。しかし、五苓散単独ではてんかん脳波に関しては抑えることはできなかったが、他の抗てんかん薬(特にレベチラセタム)と併用することで2次性てんかん発作の出現を抑制でき可能性を示した。
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