A new strategy for epilepsy therapy and Kampo: Focusing on preventing brain edema in basic research

• Project/Area Number: 26460139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Tokushima Bunri University
• Principal Investigator: Itoh Kouichi 徳島文理大学, 薬学部, 教授 (30291149)
• Co-Investigator(Kenkyū-buntansha): 石原 康宏 広島大学, 総合科学研究科, 助教 (80435073)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 漢方薬 / てんかん / 脳浮腫 / BBB / 脳内炎症 / 予防 / 五苓散 / 血管原性脳浮腫 / 側頭葉てんかんモデルマウス / MRI / てんかん原性

Outline of Final Research Achievements

In the present study, we determined that treatment with Kampo Gorei-san (GRS) after status epilepticus (SE) termination by diazepam might prevent the neurotoxicity induced by brain edema events via blood-brain barrier (BBB), and the possible molecular and cellular mechanisms of GRS treatment. To assess the effect of GRS against the brain alterations after SE, we focused on BBB dysfunction associated with angiogenesis and brain inflammation. The consecutive treatment of GRS inhibited the temporarily increased BBB leakage in the hippocampus two days after SE. These findings suggested that these brain alterations by SE-induced BBB failure were prevented by GRS treatment. Furthermore, in the acute phase of the latent period, these upregulations of pro-inflammatory-related molecules were inhibited by GRS treatment. These findings suggest that GRS is likely involved in neuroprotection via anti-inflammatory activities against BBB dysfunction in the acute phase of epileptogenesis after SE.

Research Products

• [Journal Article] Levetiracetam treatment influences blood-brain barrier failure associated with angiogenesis and inflammatory responses in the acute phase of epileptogenesis in post-status epilepticus mice (2016)
  • Author(s): Kouichi Itoh, Yasuhiro Ishihara, Rie Komori, Hiromi Nochi, Ruri Taniguchi, Yoichi Chiba, Masaki Ueno, Fuyuko Takata-Tsuji, Shinya Dohgu, Yasufumi Kataoka
  • Journal Title: Brain Research Volume: 1652 Pages: 1-13
  • DOI: 10.1016/j.brainres.2016.09.038
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeatedtreatment with high-dose levetiracetam (2015)
  • Author(s): ・Itoh, K., Inamine, M., Oshima, W., Kotani, M., Chiba, Y., Ueno, M., Ishihara, Y
  • Journal Title: Brain Reasaech Volume: 1608 Pages: 225-234
  • DOI: 10.1016/j.brainres.2015.03.005
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] てんかん原性初期に発現する脳浮腫に対する五苓散の効果 (2015)
  • Author(s): 大江 優美、石原 康宏、小森 理絵、伊藤康一
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: ザイン・クリエイティブセンター神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Status epileptics後に出現する脳浮腫に対する五苓散の効果 (2015)
  • Author(s): 伊藤 康一、大江 優美、小森 理絵、石原 康宏
  • Organizer: 香川脳神経研究会（第10回定例会）
  • Place of Presentation: ロイヤルパークホテル高松
  • Year and Date: 2015-01-16
• [Presentation] てんかん原性の五苓散による予防的治療効果の可能性の検討 (2014)
  • Author(s): 大江 優美、 稲嶺盛佳、 川真田 実来、 小森 理絵、 石原 康宏、 伊藤康一
  • Organizer: 第53回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-11-08 – 2014-11-09
• [Remarks] 薬物治療学講座 (旧分子薬理学講座) 研究概要
  • URL: http://kp.bunri-u.ac.jp/kph02/research.html
• [Remarks] 香川薬学部 薬物治療学講座
  • URL: http://kp.bunri-u.ac.jp/kph02/index.html