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Pathomechanisms and Control of Epileptogenic Foci: Imaging Practices for Surgical Specimens

Research Project

Project/Area Number 19H01061
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionNiigata University

Principal Investigator

Kakita Akiyoshi  新潟大学, 脳研究所, 教授 (80281012)

Co-Investigator(Kenkyū-buntansha) 田井中 一貴  新潟大学, 脳研究所, 教授 (80506113)
北浦 弘樹  新潟大学, 脳研究所, 特任准教授 (80401769)
藤井 幸彦  新潟大学, 脳研究所, 教授 (40283014)
前原 健寿  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (40211560)
池田 昭夫  京都大学, 医学研究科, 特定教授 (90212761)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2021: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2020: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2019: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Keywordsてんかん / 神経回路 / 3D / 脳透明化 / フラビン蛍光イメージング / 脳機能外科 / 神経病理
Outline of Research at the Start

てんかん焦点では、どのように異常な神経興奮が惹起され伝播するのか?この命題はいわば、臨床てんかん学における古典的かつ本質的命題である。本研究では、この命題に対する明確な‘解’を提供し、難治てんかん患者に対する新たな外科的/内科的治療戦略を開発する。研究戦略の柱は、外科的に切除されたてんかん焦点脳組織を対象に行う“生鮮脳スライスを用いた生理学的解析”と“脳組織の3次元的病理解析”である。ここから時空間的興奮動態の特徴を捉え、薬理作用を検証し、神経細胞やグリア細胞のネットワーク基盤を明らかにする。つまり、最新鋭の解析技術で機能と形態を統合するイメージング・プラクティスである。

Outline of Final Research Achievements

How is abnormal neural excitation elicited and propagated in epileptogenic brain lesions? In this study, we performed physiological analysis using fresh brain slices and three-dimensional pathological analysis of epileptic focal brain tissue that had been surgically removed. The physiological analysis was performed using an originally developed flavin fluorescence imaging method, and the morphological analysis was performed using a newly developed tissue clearing technique for human brain slices. From this analysis, we characterized the spatiotemporal excitation dynamics, verified the pharmacological effects, and clarified the network basis of neurons and glial cells.

Academic Significance and Societal Importance of the Research Achievements

てんかんは罹患率の高い症候群である。てんかん焦点が臨床的に同定される薬剤抵抗性の局在性難治性てんかん患者に対し、外科的焦点切除術が行われることがある。てんかん焦点では異常な神経興奮がどのように惹起され伝播するのか?これはいわば臨床てんかん学における古典的かつ本質的命題である。本研究では、このてんかん病態機序を理解するために、最新鋭の解析技術で機能異常と形態異常の実態を明らかにした。本研究の成果は、難治てんかん患者に対する新たな外科的/内科的治療戦略を開発するための重要な知見となった。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Comments on the Screening Results   Annual Research Report
  • Research Products

    (35 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 9 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 10 results) Book (2 results)

  • [Int'l Joint Research] トロント小児病院(カナダ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Burden of seizures and comorbidities in patients with epilepsy: a survey based on the tertiary hospital-based Epilepsy Syndrome Registry in Japan.2022

    • Author(s)
      Inoue Y, Hamano SI, Hayashi M, Sakuma H, Hirose S, Ishii A, Honda R, Ikeda A, Imai K, Jin K, Kada A, Kakita A, Kato M, Kawai K, Kawakami T, Kobayashi K, Matsuishi T, Matsuo T, Nabatame S, Okamoto N, Ito S, Okumura A, Saito A, Shiraishi H, Shirozu H, Saito T, Sugano H, Takahashi Y, Yamamoto H, Fukuyama T, Kuki I.
    • Journal Title

      Epileptic Disord

      Volume: 24 Issue: 1 Pages: 82-94

    • DOI

      10.1684/epd.2021.1361

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sirolimus for epileptic seizures associated with focal cortical dysplasia type II.2022

    • Author(s)
      Kato M, Kada A, Shiraishi H, Tohyama J, Nakagawa E, Takahashi Y, Akiyama T, Kakita A, Miyake N, Fujita A, Saito AM, Inoue Y.
    • Journal Title

      Ann Clin Transl Neurol

      Volume: 9 Issue: 2 Pages: 181-192

    • DOI

      10.1002/acn3.51505

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson’s disease.2021

    • Author(s)
      Matsui, H.*, Ito, J., Matsui, N., Uechi, T., Onodera, O., Kakita, A.
    • Journal Title

      Nat. Commun.

      Volume: - Issue: 1 Pages: 3101-3101

    • DOI

      10.1038/s41467-021-23452-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic variations and neuropathologic features of patients with PARK2.2021

    • Author(s)
      Seike N, Yokoseki A, Takeuchi R, Saito K, Miyahara H, Miyashita A, Ikeda T, Aida I, Nakajima T, Kanazawa M, Wakabayashi M, Toyoshima Y, Takahashi H, Matumoro R, Toda T, Onodera O, Ishikawa A, Ikeuchi T, Kakita A.
    • Journal Title

      Mov Disord

      Volume: 36 Issue: 7 Pages: 1634-1643

    • DOI

      10.1002/mds.28521

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current medico-psycho-social conditions of patients with West syndrome in Japan2021

    • Author(s)
      Yoshitomi S, Hamano SI, Hayashi M, ... Matsuo T (18/32), et al
    • Journal Title

      Epileptic Disord

      Volume: 23 Issue: 4 Pages: 579-589

    • DOI

      10.1684/epd.2021.1301

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reactive astrocytes contribute to epileptogenesis in patients with cavernous angioma2021

    • Author(s)
      Kitaura H, Hiraishi T, Itoh Y, Oishi M, Fujii Y, Fukuda M, Kakita A.
    • Journal Title

      Epilepsy Res

      Volume: 176 Pages: 106732-106732

    • DOI

      10.1016/j.eplepsyres.2021.106732

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure-based classification of tauopathies2021

    • Author(s)
      Shi Yang、Zhang Wenjuan、Yang Yang、Tanaka Hidetomo、Kakita Akiyoshi、Ikeuchi Takeshi、Kovacs Gabor G.、Revesz Tamas、Ghetti Bernardino、Hasegawa Masato、Goedert Michel、Scheres Sjors H. W. et al.
    • Journal Title

      Nature

      Volume: 598 Issue: 7880 Pages: 359-363

    • DOI

      10.1038/s41586-021-03911-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deep learning-based diagnosis of temporal lobe epilepsy associated with hippocampal sclerosis: An MRI study2021

    • Author(s)
      Ito Y, Fukuda M, Matsuzawa H, Masuda H, Kobayashi Y, Hasegawa N, Kitaura H, Kakita A, Fujii Y.
    • Journal Title

      Epilepsy Res

      Volume: 178 Pages: 106815-106815

    • DOI

      10.1016/j.eplepsyres.2021.106815

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 海馬硬化症のてんかん原性.2021

    • Author(s)
      北浦弘樹、柿田明美.
    • Journal Title

      Epilepsy

      Volume: 15 Pages: 74-77

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Surgical strategy for focal cortical dysplasia based on the analysis of the spike onset and peak zones on magnetoencephalography.2020

    • Author(s)
      Shirozu H, Hashizume A, Masuda H, Kakita A, Otsubo H, Kameyama S.
    • Journal Title

      J Neurosurg

      Volume: 133 Issue: 6 Pages: 1850-1862

    • DOI

      10.3171/2019.6.jns191058

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic profile differentiating between mesial temporal lobe epilepsy with and without hippocampal sclerosis2020

    • Author(s)
      Furukawa Ayako、Kakita Akiyoshi、Chiba Yoichi、Kitaura Hiroki、Fujii Yukihiko、Fukuda Masafumi、Kameyama Shigeki、Shimada Atsuyoshi
    • Journal Title

      Epilepsy Research

      Volume: 168 Pages: 106502-106502

    • DOI

      10.1016/j.eplepsyres.2020.106502

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues2020

    • Author(s)
      Susaki Etsuo A.、Shimizu Chika、Kuno Akihiro、Tainaka Kazuki、Li Xiang、Shibayama Mitsuhiro、Ueda Hiroki R. et al.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1982-1982

    • DOI

      10.1038/s41467-020-15906-5

    • NAID

      120006956725

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation.2019

    • Author(s)
      Inoue M, Saito R, Kakita A, Tainaka K.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 29 Issue: 15 Pages: 1886-1890

    • DOI

      10.1016/j.bmcl.2019.05.049

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The epileptogenic zone in pharmacy-resistant temporal lobe epilepsy with amygdala enlargement.2019

    • Author(s)
      Suzuki H, Sugano H, Nakajima M, Higo T, Iimura Y, Mitsuhashi T, Fusegi K, Kakita A, Otsubo H, Arai H.
    • Journal Title

      Epileptic Disord

      Volume: 21 Pages: 252-264

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multiplex ligation-dependent probe amplification analysis is useful for detecting a copy number gain of the FGFR1 tyrosine kinase domain in dysembryoplastic neuroepithelial tumors.2019

    • Author(s)
      Matsumura N, Nobusawa S, Ito J, Kakita A, Suzuki H, Fujii Y, Fukuda M, Iwasaki M, Nakasato N, Tominaga T, Natsume A, Mikami Y, Shinojima N, Yamazaki T, Nakazato Y, Hirato J, Yokoo H.
    • Journal Title

      J Neurooncol.

      Volume: 143 Issue: 1 Pages: 27-33

    • DOI

      10.1007/s11060-019-03138-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] てんかんの外科病理.2021

    • Author(s)
      柿田明美
    • Organizer
      第54回 日本てんかん学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 若手の神経化学会員の皆様へのメッセージ:神経病理学会から.2021

    • Author(s)
      柿田明美
    • Organizer
      第64回日本神経化学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 神経病理からのてんかん病態へのアプローチ.2021

    • Author(s)
      北浦弘樹、柿田明美
    • Organizer
      第62回 日本神経学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Morphological and functional features associated with epileptogenesis in the hippocampus of MTLE.2021

    • Author(s)
      Kitaura H, Itoh Y, Fukuda M, Tainaka K, Fujii Y, Kakita A.
    • Organizer
      第62回 日本神経病理学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 経過中に発作型と脳波所見の変容を示した側頭葉astrocytomaの小児例.2021

    • Author(s)
      放上萌美,遠山潤,小林悠,大野武,岡崎健一,平岩明子,増田浩,福多真史,柿田明美.
    • Organizer
      第54回日本てんかん学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 海馬硬化症のてんかん原性:外科病理標本を用いた機能異常と形態異常の接点.2021

    • Author(s)
      北浦弘樹、柿田明美.
    • Organizer
      第54回日本てんかん学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] てんかんの外科病理2021

    • Author(s)
      柿田明美.
    • Organizer
      第44回 日本てんかん外科学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 3D pathology of cerebral amyloid antipathy based on tissue clearing technique.2020

    • Author(s)
      Inoue M, Saito R, Kakita A, Tainaka K.
    • Organizer
      第61回日本神経病理学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 結節性硬化症のてんかん焦点組織特性.2020

    • Author(s)
      北浦弘樹、福多真史、藤井幸彦、柿田明美.
    • Organizer
      第61回日本神経病理学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 小児神経疾患の病理学:症例に学ぶ病態2020

    • Author(s)
      柿田明美
    • Organizer
      日本小児神経学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] てんかん外科病理学の実際:症例から学ぶ病態2020

    • Author(s)
      柿田明美
    • Organizer
      第11回 アルツハイマー病とてんかんを考える会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 3D神経病理学に向けたホールマウント染色手法の開発.2019

    • Author(s)
      田井中一樹、齋藤理恵、井上雅文、柿田明美.
    • Organizer
      第60回日本神経病理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Visualization of epileptic activities in human brain slices ex vivo.2019

    • Author(s)
      Kitaura H, Fukuda M, Fujii Y, Kakita A.
    • Organizer
      Neuro2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Epileptogenesis of the subiculum associated with hippocampal sclerosis in patients with MTLE: ex vivo optical imaging study.2019

    • Author(s)
      Kitaura H, Shirozu H, Masuda H, Fukuda M, Fujii Y, Kakita A.
    • Organizer
      SfN Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathophysiological characteristics associated with epileptogenesis: imaging of human brain slices.2019

    • Author(s)
      Kakita A.
    • Organizer
      Infantile Seizure Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 精神神経機能障害としての‘てんかん’:病態機序を神経病理学からさぐる.2019

    • Author(s)
      柿田明美.
    • Organizer
      第115回日本精神神経学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] てんかん外科病理学の実際:症例から学ぶ病態.2019

    • Author(s)
      柿田明美.
    • Organizer
      日本てんかん学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Book] てんかん専門医ガイドブック 改定第2版 - てんかんにかかわる医師のための基本知識 -2020

    • Author(s)
      柿田明美(共著)
    • Total Pages
      433
    • Publisher
      診断と治療社
    • ISBN
      9784787824172
    • Related Report
      2020 Annual Research Report
  • [Book] てんかん専門医ガイドブック 改定第2版2020

    • Author(s)
      柿田明美(共著)
    • Publisher
      診断と治療社
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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