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Analysis of new pathological phenomena in adult onset temporal lobe epilepsy and the potential therapeutic effect of glycated protein expression control

Research Project

Project/Area Number 17K10908
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionJuntendo University

Principal Investigator

NAKAJIMA MADOKA  順天堂大学, 医学部, 准教授 (50317450)

Co-Investigator(Kenkyū-buntansha) 宮嶋 雅一  順天堂大学, 医学部, 教授 (60200177)
新井 一  順天堂大学, 医学部, 教授 (70167229)
西村 欣也  順天堂大学, 医学部, 教授 (80164581)
菅野 秀宣  順天堂大学, 医学部, 先任准教授 (90265992)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脳内環境 / 認知機能 / 側頭葉てんかん / ロイシンリッチα2グリコプロテイン / ピロカルピン酸 / パッチクランプ / 長期増強 / 予防医学 / 扁桃体腫大 / 炎症メディエーター / 糖化蛋白 / てんかん原性 / 扁桃体 / 海馬 / てんかん原生 / 脳波 / 神経科学 / トランスレーショナルリサーチ / 病理学
Outline of Final Research Achievements

We verified the preventative effects of increasing the expression of leucine-rich alpha2 glycoprotein (LRG1) in the brain regarding the decline of cognitive function caused by epileptic seizures using an animal model of secondary temporal lobe epilepsy (TLE). Electrophysiological and molecular biological analyses were performed on adult secondary epileptogenic formation using an animal model of TLE induced with pilocarpine utilizing CAG-loxP-GFP-loxP-LRG1 transgenic mice (LRG-Tg). The cognitive behavioral experiments indicated a significant decline in cognitive function and significant reduction in LTP was confirmed in the control mouse after status epilepticus (SE). Neural dropout in the CA1 region of the hippocampus was particularly marked. However, LTP reduction was not observed in the LRG-Tg mice after SE. LRG1 expression in the hippocampus was confirmed to suppress nerve cell firing and prevent cognitive function decline after SE.

Academic Significance and Societal Importance of the Research Achievements

疾患耐性に対する脳内環境に関する研究は,後天的に発症する神経疾患に対する予防的対策となる。後天性疾患である側頭葉てんかんに対して,発症を予防し,かつ認知機能を維持する脳内環境を考察した学術的意義の高い研究である。本研究は,糖化蛋白であるロイシンリッチα2グリコプロテインが増加した脳内環境下では,けいれん重積からてんかん原性が形成されることを予防し,認知機能を保つことを証明した。側頭葉てんかんの発症を抑止する脳保護作用をもつ脳内環境を安全に提供することができれば,創薬へ発展する可能性がある。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (35 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (15 results) (of which Int'l Joint Research: 7 results) Book (2 results) Remarks (2 results)

  • [Int'l Joint Research] University of Toronto(カナダ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Eastern Finland/Kuopio University/Oulu University(フィンランド)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Extent of Leptomeningeal Capillary Malformation is Associated With Severity of Epilepsy in Sturge-Weber Syndrome2021

    • Author(s)
      Sugano Hidenori、Iimura Yasushi、Igarashi Ayuko、Nakazawa Mika、Suzuki Hiroharu、Mitsuhashi Takumi、Nakajima Madoka、Higo Takuma、Ueda Tetsuya、Nakanishi Hajime、Niijima Shinichi、Karagiozov Kostadin、Arai Hajime
    • Journal Title

      Pediatric Neurology

      Volume: 117 Pages: 64-71

    • DOI

      10.1016/j.pediatrneurol.2020.12.012

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated CSF LRG and Decreased Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus2021

    • Author(s)
      Vanninen Aleksi、Nakajima Madoka、Miyajima Masakazu、Rauramaa Tuomas、Kokki Merja、Musialowicz Tadeusz、Makinen Petra M.、Herukka Sanna-Kaisa、Koivisto Anne M.、Jaaskelainen Juha E.、Hiltunen Mikko、Leinonen Ville
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 5 Pages: 1105-1105

    • DOI

      10.3390/jcm10051105

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus2020

    • Author(s)
      Nakajima M.、Rauramaa T.、Makinen P. M.、Hiltunen M.、Herukka S.‐K.、Kokki M.、Musialowicz T.、Jyrkkanen H.‐K.、Danner N.、Junkkari A.、Koivisto A. M.、Jaaskelainen J. E.、Miyajima M.、Ogino I.、Furuta A.、Akiba C.、Kawamura K.、Kamohara C.、Sugano H.、Tange Y.、Karagiozov K.、Leinonen V.、Arai H.
    • Journal Title

      European Journal of Neurology

      Volume: 28 Issue: 2 Pages: 389-400

    • DOI

      10.1111/ene.14575

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuropsychological tests are useful for predicting comorbidities of idiopathic normal pressure hydrocephalus2020

    • Author(s)
      Kamohara Chihiro、Nakajima Madoka、Kawamura Kaito、Akiba Chihiro、Ogino Ikuko、Xu Hanbing、Karagiozov Kostadin、Arai Hajime、Miyajima Masakazu
    • Journal Title

      Acta Neurologica Scandinavica

      Volume: 142 Issue: 6 Pages: 623-631

    • DOI

      10.1111/ane.13306

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional MRI and Structural Connectome Analysis of Language Networks in Japanese-English Bilinguals2020

    • Author(s)
      Mitsuhashi Takumi、Sugano Hidenori、Asano Keiko、Nakajima Takayuki、Nakajima Madoka、Okura Hidehiro、Iimura Yasushi、Suzuki Hiroharu、Tange Yuichi、Tanaka Toshihisa、Aoki Shigeki、Arai Hajime
    • Journal Title

      Neuroscience

      Volume: 431 Pages: 17-24

    • DOI

      10.1016/j.neuroscience.2020.01.030

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Deep Learning Approach with a 3D Convolutional Ladder Network for Differential Diagnosis of Idiopathic Normal Pressure Hydrocephalus and Alzheimer’s Disease2020

    • Author(s)
      Irie Ryusuke、Otsuka Yujiro、Hagiwara Akifumi、Kamagata Koji、Kamiya Kouhei、Suzuki Michimasa、Wada Akihiko、Maekawa Tomoko、Fujita Shohei、Kato Shimpei、Nakajima Madoka、Miyajima Masakazu、Motoi Yumiko、Abe Osamu、Aoki Shigeki
    • Journal Title

      Magnetic Resonance in Medical Sciences

      Volume: 19 Issue: 4 Pages: 351-358

    • DOI

      10.2463/mrms.mp.2019-0106

    • NAID

      130007948913

    • ISSN
      1347-3182, 1880-2206
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Epileptogenic Zone in Pharmaco-Resistant Temporal Lobe Epilepsy With Amygdala Enlargement2019

    • Author(s)
      Hiroharu Suzuki, Hidenori Sugano, Madoka Nakajima, Takuma Higo, Yasushi Iimura, Takumi Mitsuhashi, Keiko Fusegi, Akiyoshi Kakita, Hiroshi Otsubo, Hajime Arai
    • Journal Title

      Epileptic Disorders

      Volume: 21 Pages: 252-264

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Is decremental modulation index on scalp EEG a sign of good seizure outcome? A Sturge-Weber syndrome case with epileptic spasms2019

    • Author(s)
      Iimura Yasushi、Sugano Hidenori、Nakajima Madoka、Higo Takuma、Suzuki Hiroharu、Mitsuhashi Takumi、Ueda Tetsuya、Karagiozov Kostadin、Igarashi Ayuko、Otsubo Hiroshi、Arai Hajime
    • Journal Title

      Clinical Neurophysiology

      Volume: 130 Issue: 9 Pages: 1499-1501

    • DOI

      10.1016/j.clinph.2019.06.002

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

    • Author(s)
      Hiroharu Suzuki, Hidenori Sugano, Madoka Nakajima, Takuma Higo, Yasushi Iimura, Takumi Mitsuhashi, Keiko Fusegi, Akiyoshi Kakita, Hiroshi Otsubo, Hajime Arai
    • Journal Title

      Epileptic Disord

      Volume: 印刷中

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preoperative phosphorylated tau measurement of cerebrospinal fluid can predict cognitive function 3 years after shunt surgery in patients with idiopathic normal pressure hydrocephalus.2018

    • Author(s)
      Madoka Nakajima, Masakazu Miyajima, Ikuko Ogino, Chihiro Akiba, Kaito Kawamura, Yoshinao Harada, Takeshi Hara, Hidenori Sugano, Kostadin Karagiozov, Takeshi Ikeuchi, Takahiko Tokuda, Hajime Arai
    • Journal Title

      J Alzheimers Dis.

      Volume: 66 Issue: 1 Pages: 319-331

    • DOI

      10.3233/jad-180557

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Change of Amyloid-β 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus2018

    • Author(s)
      Akiba C, Nakajima M, Miyajima M, Ogino I, Motoi Y, Kawamura K, Adachi S, Kondo A, Sugano H, Tokuda T, Irie K, Arai H
    • Journal Title

      J Alzheimers Dis.

      Volume: 25 Issue: 3 Pages: 989-1002

    • DOI

      10.3233/jad-180059

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leucine-rich α2-glycoprotein overexpression in the brain contributes to memory impairment2017

    • Author(s)
      2.Akiba C, Nakajima M, Miyajima M, Ogino I, Miura M, Inoue R, Nakamura E, Kanai F, Tada N, Kunichika M, Yoshida M, Nishimura K, Kondo A, Sugano H, Arai H.
    • Journal Title

      Neurobiology of Aging

      Volume: 60 Pages: 11-19

    • DOI

      10.1016/j.neurobiolaging.2017.08.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rescue Pallidal Stimulation for Diphasic and Stimulation induced Dyskinesia after Successful Subthalamic Stimulation for Parkinson’s Disease2017

    • Author(s)
      Nakajima A, Oyama G, Jo T, Shimo Y, Umemura A, Nakajima M, Ishii H, Arai H, Hattori N
    • Journal Title

      Neurology and Clinical Neuroscience

      Volume: 5 Issue: 4 Pages: 127-128

    • DOI

      10.1111/ncn3.12127

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Two Odd Targets” Strategy in Deep Brain Stimulation for Parkinson’s Disease With Unilateral Levodopa Induced Dystonia.2017

    • Author(s)
      Sekimoto S, Oyama G, Jo T, Nakajima A, Shimo Y, Nakajima M, Umemura A, Ito M, Arai H, Hattori N
    • Journal Title

      Neurology and Clinical Neuroscience

      Volume: 5 Issue: 4 Pages: 129-130

    • DOI

      10.1111/ncn3.12131

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Expression of the glycated protein leucine-rich alpha2 glycoprotein in the hippocampus prevents decreased cognitive function after status epilepticus2019

    • Author(s)
      Madoka Nakajima, Hidenori Sugano, Takuma Higo, Yasushi Iimura, Takumi Mitsuhashi, Hajime Arai
    • Organizer
      The 33rd International Epilepsy Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Expression of leucine-rich alpha2 glycoprotein in the hippocampus prevents decreased cognitive function after status epilepticus2019

    • Author(s)
      中島 円, 菅野秀宣, 肥後拓磨,飯村康司,三橋 匠,川村海渡,新井 一
    • Organizer
      第53回日本てんかん学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Expression of leucine-rich alpha2 glycoprotein in the hippocampus prevents decreased cognitive function after status epilepticus2019

    • Author(s)
      Madoka Nakajima, Hidenori Sugano, Takuma Higo, Yasushi Iimura, Takumi Mitsuhashi, Kaito Kawamura, Hajime Arai
    • Organizer
      AES2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Amygdala is not an actual epileptic focus in temporal lobe epilepsy associated with amygdala enlargement.2018

    • Author(s)
      Hiroharu Suzuki, Hidenori Sugano, Madoka Nakajima, Takuma Higo, Yasushi Iimura, Takumi Mitsuhashi, Keiko Fusegi, Akiyoshi Kakita, Hiroshi Otsubo, Hajime Arai
    • Organizer
      2018 Annual Meeting of the American Epilepsy Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Brain Localization of Leucine-Rich a2-Glycoprotein and Role.2018

    • Author(s)
      Nakajima M
    • Organizer
      8th Kuopio Alzheimer Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Leucine-rich α2-glycoprotein overexpression in the brain contribute to age-related memory impairment.2018

    • Author(s)
      Nakajima M, Akiba C, Miyajima M
    • Organizer
      FENS 11th Forum of Neuroscience
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 内側側頭葉てんかんにおける高周波律動解析を用いた術中皮質脳波診断の有用性の検討2018

    • Author(s)
      鈴木 皓晴,菅野秀宣,中島 円
    • Organizer
      第41回日本てんかん外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Management of hydrocephalus after hemispherotomy for Sturge-Weber syndrome: 3 case reports2017

    • Author(s)
      Madoka Nakajima
    • Organizer
      IFNE World Congress of Neuroendoscopy 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 半球離断後の水頭症管理: 4症例報告2017

    • Author(s)
      中島 円, 菅野秀宣, 宮嶋雅一, 新井 一
    • Organizer
      第24回日本神経内視鏡学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 包括的てんかん治療における迷走神経刺激療法の役割~順天堂大学てんかんセンターでの症例と治療成績2017

    • Author(s)
      中島 円
    • Organizer
      第26回J・K・Wフォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] 運動野を含む皮質形成異常に対する難治性てんかんの治療ストラテジー2017

    • Author(s)
      鈴木 皓晴,菅野秀宣,中島 円
    • Organizer
      第11回日本てんかん学会関東甲信越地方会
    • Related Report
      2017 Research-status Report
  • [Presentation] Therapeutic outcome of 101 patients with Sturge-Weber syndrome and effective diagnostic modalities for identifying seizure severity and epileptic zone.2017

    • Author(s)
      鈴木 皓晴,菅野秀宣,中島 円
    • Organizer
      第59回日本小児神経学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 扁桃体腫大による側頭葉てんかんにおける術中脳波での高周波律動の検出と手術結果の検討2017

    • Author(s)
      鈴木 皓晴,菅野秀宣,中島 円
    • Organizer
      日本脳神経外科学会第76回学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] The examination of surgical procedures and seizure outcome in a case of temporal lobe epilepsy with amygdala enlargement2017

    • Author(s)
      鈴木 皓晴,菅野秀宣,中島 円
    • Organizer
      第51回日本てんかん学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Hippocampus is the epileptogenic zone in patents with temporal lobe epilepsy secondary to amygdala enlargement.2017

    • Author(s)
      鈴木 皓晴,菅野秀宣,中島 円
    • Organizer
      2017 Annual Meeting of the American Epilepsy Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] デバイスとITを使いこなす脳神経外科手術2017

    • Author(s)
      梅村 淳、中島 円
    • Total Pages
      151
    • Publisher
      メジカルビュー社
    • ISBN
      9784758315692
    • Related Report
      2017 Research-status Report
  • [Book] 臨床画像:特発性正常圧水頭症 (iNPH) の病態 : バイオマーカーと治療2017

    • Author(s)
      中島 円、宮嶋雅一
    • Publisher
      メジカルビュー社
    • Related Report
      2017 Research-status Report
  • [Remarks] 機能Group/順天堂大学

    • URL

      https://functionalneurosurgeryjuntendouniversity.wordpress.com

    • Related Report
      2018 Research-status Report
  • [Remarks] 順天堂大学医学部附属順天堂医院てんかんセンター

    • URL

      https://www.juntendo.ac.jp/hospital/clinic/epilepsy/

    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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