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Inflammation and ischemia are Involved in the onset of epilepsy

Research Project

Project/Area Number 26462217
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, 先任准教授 (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, 准教授 (90265992)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsてんかん原性 / 慢性炎症 / 海馬 / パッチクランプ / 糖タンパク質 / てんかん原生 / トランスジェニックマウス / 長期増強 / ピロカルピン酸 / ロイシン / てんかん抑制 / Long-term potentiation / 認知機能 / ロイシンリッチリピート
Outline of Final Research Achievements

Inflammation of the brain has received widespread attention as an important factor in acquired epileptogenicity. Our clinical study suggested that expression of HMGB1 and TLR4 increases in epileptogenic lesion. HMGB1-TLR4 pathway also plays an important part in human epileptogenesis. It was discovered that in human epileptgenic hippocampus, HMGB1 acts chronically in localized areas and TLR4 becomes involved. On the other hand, leucine-rich alpha-2-glycoprotein (LRG1)therefore is implicated and expresses increasingly in a variety of physiological reactions, especially in inflammatory-related reactions. LRG gene [LRG1] was produced under a GFAP promoter in order to study the conditional overexpression of LRG in the brain. Electrophysiological characterization was used to analyze. The slopes of fEPSPs were significantly smaller in LRG-Tg mice than controls (p < 0.01), indicating an impairment of synaptic transmission in LRG-Tg mice.LRG may work on epileptic seizure deterrence.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (45 results)

All 2016 2015 2014 Other

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (27 results) (of which Int'l Joint Research: 5 results) Book (4 results) Remarks (1 results)

  • [Journal Article] Analysis of Epileptic Discharges from Implanted Subdural Electrodes in Patients with Sturge-Weber Syndrome2016

    • Author(s)
      Yasushi Iimura, Hidenori Sugano, Madoka Nakajima, Takuma Higo, Hiroharu Suzuki, Hajime
    • Journal Title

      PLos One

      Volume: April 7 Issue: 4 Pages: 1-10

    • DOI

      10.1371/journal.pone.0152992

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FDG-PET with 3D-SSP predictive value of surgical outcome in patients with temporal lobe epilepsy2016

    • Author(s)
      Takuma Higo, Hidenori Sugano, Madoka Nakajima, Kostadin Karagiozov, Yasushi Iimura, Masaru Suzuki, Kiyoshi Sato, and Hajime Arai
    • Journal Title

      Seizure

      Volume: 41 Pages: 127-133

    • DOI

      10.1016/j.seizure.2016.07.019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential MicroRNA Biomarkers for the Diagnosis of Idiopathic Normal Pressure Hydrocephalus2016

    • Author(s)
      Ivana Jurjevic, Masakazu Miyajima, Ikuko Ogino, Chihiro Akiba, Madoka Nakajima, Akihide Kondo, Kikkawa Mika, Nobutaka Hattori, Hajime Arai
    • Journal Title

      Journal of Alzheimer Disease

      Volume: 56 Issue: 1 Pages: 317-325

    • DOI

      10.3233/jad-160848

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dural Enhancement in a Patient with Sturge-Weber Syndrome Revealed by Double Inversion Recovery Contrast Using Synthetic MRI2016

    • Author(s)
      Hagiwara A, Nakazawa M, Andica C, Tsuruta K, Takano N, Hori M, Suzuki H, Sugano H, Arai H, Aoki S.
    • Journal Title

      Magnetic Resonance in Medical Sciences

      Volume: 15 Issue: 2 Pages: 151-152

    • DOI

      10.2463/mrms.ci.2015-0066

    • NAID

      130005144176

    • ISSN
      1347-3182, 1880-2206
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epilepsy Surgery for Pediatric Epilepsy: Optimal Timing of Surgical Intervention2015

    • Author(s)
      Hidenori Sugano, Hajime Arai
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 55 Issue: 5 Pages: 399-406

    • DOI

      10.2176/nmc.ra.2014-0369

    • NAID

      130005069871

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebrospinal Fluid Biomarkers for Prognosis of Long-Term Cognitive Treatment Outcomes in Patients with Idiopathic Normal Pressure Hydrocephalus2015

    • Author(s)
      Nakajima M, Miyajima M, Ogino I, Akiba C, Sugano H, Karagiozov K, Domon N, Arai H
    • Journal Title

      Journal of Neurological Science

      Volume: 357 Issue: 1-2 Pages: 88-95

    • DOI

      10.1016/j.jns.2015.07.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Use of external lumbar cerebrospinal fluid drainage and lumboperitoneal shunts with Strata NSC valves in idiopathic normal pressure hydrocephalus: a single-center experience2015

    • Author(s)
      Nakajima M, Miyajima M, Ogino I, Sugano H, Akiba C, Miyata H, Karagiozov KL, Arai H
    • Journal Title

      World Neurosurgery

      Volume: 83 Issue: 3 Pages: 387-393

    • DOI

      10.1016/j.wneu.2014.08.004

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Impact of cerebrospinal shunting for idiopathic normal pressure hydrocephalus on the amyloid cascade2015

    • Author(s)
      M Moriya, M Miyajima, M Nakajima, I Ogino, H Arai
    • Journal Title

      Plos One

      Volume: 357 Issue: 3 Pages: 88-95

    • DOI

      10.1371/journal.pone.0119973

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 頭蓋内海綿状血管腫周辺の頭蓋内電極脳波所見と病理所見からみるてんかん原性獲得機序の仮説2015

    • Author(s)
      中島 円,菅野秀宣, 原田佳尚,飯村康司,肥後拓磨,新井 一
    • Journal Title

      日本薬物脳波学会雑誌

      Volume: 16 Pages: 35-41

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Evolution of a symptomatic diffuse developmental venous anomaly with progressive cerebral atrophy in an atypical case of Sturge-Weber syndrome.2014

    • Author(s)
      Ohno K, Saito Y, Togawa M, Shinohara Y, Ito T, Sugano H, Itamura S, Nishimura Y, Tamasaki A, Maegaki Y.
    • Journal Title

      Brain Dev.

      Volume: - Issue: 8 Pages: 817-821

    • DOI

      10.1016/j.braindev.2014.12.003

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sturge–Weber syndrome with spontaneous intracerebral hemorrhage in childhood.2014

    • Author(s)
      M Nakajima, H Sugano, Y Iimura, T Higo, H Nakanishi, K Shimoji, K Karagiozov, M Miyajima, H Arai
    • Journal Title

      Neurosurg Pediatr.

      Volume: 13(1) Issue: 1 Pages: 90-93

    • DOI

      10.3171/2013.9.peds133

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Posterior quadrant disconnection surgery for Sturge-Weber syndrome.2014

    • Author(s)
      Sugano H, Nakanishi H, Nakajima M, Higo T, Iimura Y, Tanaka K, Hosozawa M, Niijima S, Arai H
    • Journal Title

      Epilepsia

      Volume: In Press Issue: 5 Pages: 683-9

    • DOI

      10.1111/epi.12547

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge-Weber syndrome.2014

    • Author(s)
      Nakashima M, Miyajima M, Sugano H, Iimura Y, Kato M, Tsurusaki Y, Miyake N, Saitus H, Arai H, Matsumoto N.
    • Journal Title

      J Hum Genet.

      Volume: 59 Issue: 12 Pages: 691-3

    • DOI

      10.1038/jhg.2014.95

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Ischemia and Inflammation are Involved in the Onset of Epilepsy in Sturge-Weber Syndrome. America Epilepsy Society.2016

    • Author(s)
      Madoka Nakajima, Hidenori Sugano, Hiroharu Suzuki, Yasushi Iimura, Takuma Higo, Takumi Mitsuhashi, Hajime Arai
    • Organizer
      America Epilepsy Society. 70th annual meeting
    • Place of Presentation
      Houston, Texas, George R. Brown Convention Center,
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 扁桃体腫大を伴う側頭葉てんかん患者における発作と神経心理検査の検討2016

    • Author(s)
      鈴木皓晴、菅野秀宣、中島円、肥後拓磨、飯村康司、三橋匠、新井一
    • Organizer
      日本脳神経外科学会第75回総会
    • Place of Presentation
      福岡、福岡国際会議場
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Classification and therapeutic outcome in 96 cases with Sturge-Weber syndrome2016

    • Author(s)
      Madoka Nakajima, Hidenori Sugano, Hiroharu Suzuki, Takuma Higo, Hajime Arai
    • Organizer
      The 12th European Congress on Epileptology
    • Place of Presentation
      Prague, Prague Congress Centre
    • Year and Date
      2016-09-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] スタージ・ウェバー症候群のてんかん発症には虚血と炎症が関与する2016

    • Author(s)
      中島 円
    • Organizer
      平成27年度老人性疾患病態治療研究センター研究発表会
    • Place of Presentation
      東京:順天堂大学
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 難治性てんかんを有するスタージ・ウェバー症候群の病理組織解析2016

    • Author(s)
      中島 円、菅野 秀宣、飯村 康司、肥後 拓磨、新井 一
    • Organizer
      第39回日本てんかん外科学会
    • Place of Presentation
      仙台:江陽グランドホテル
    • Year and Date
      2016-01-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 加齢による認知機能低下の原因を探る-Leucine-rich alpha-2-glycoprotein(LRG)の解析2016

    • Author(s)
      秋葉ちひろ、中島 円、宮嶋雅一、荻野郁子、新井 一、中村衣里、多田昇弘、国近美幸、吉田光孝、三浦正巳
    • Organizer
      日本老年脳神経外科学会
    • Place of Presentation
      奈良、奈良ホテル
    • Related Report
      2016 Annual Research Report
  • [Presentation] スタージ・ウェバー症候群96例における血管腫の範囲と各分類別治療成績2016

    • Author(s)
      中島 円、菅野秀宣、安部信平、池野充、五十嵐鮎子、中澤美賀、新島新一、山下進太郎
    • Organizer
      第58回 日本小児神経学会
    • Place of Presentation
      東京、京王プラザホテル
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脳内Leucine-Rich alpha-2 Glycoproteinの蓄積が認知障害を発現させる2016

    • Author(s)
      中島 円
    • Organizer
      日本老年医学学術集会
    • Place of Presentation
      金沢、ANAクラウンプラザホテル金沢
    • Related Report
      2016 Annual Research Report
  • [Presentation] irritative zone を加味したglioneuronal tumorの手術治療成績2016

    • Author(s)
      中島 円、菅野秀宣、鈴木晧晴、肥後拓磨、原 毅、下地一彰、宮嶋雅一、新井 一
    • Organizer
      第44回日本小児神経外科学会
    • Place of Presentation
      つくば, つくば国際会議場
    • Related Report
      2016 Annual Research Report
  • [Presentation] Activation of the HMGB1/ TLR signaling pathway in surrounding tissues of a frontal lobe cavernous angioma that triggered ictal asystole.2015

    • Author(s)
      M. Nakajima, H. Sugano, Y Iimura, T. Higo, Y. Harada, I. Ogino, M. Miyajima, H. Arai
    • Organizer
      69th Annual Meeting of the American Epilepsy Society
    • Place of Presentation
      Philadelphia, Pennsylvania Convention Center
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] FDG-PET with 3D-SSP predictive value of surgical outcome in patients with temporal lobe epilepsy2015

    • Author(s)
      Takuma Higo , Hidenori Sugano, Madoka Nakajima, Kostadin Karagiozov, Yasushi Iimura, Masaru Suzuki, Kiyoshi Sato, and Hajime Arai
    • Organizer
      69th Annual Meeting of the American Epilepsy Society
    • Place of Presentation
      Philadelphia, Pennsylvania Convention Center
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Obstruction of the foramen of Monro is a cause of hydrocephalus after hemispherotomy2015

    • Author(s)
      Sugano H, Nakajima M, Iimutra Y, Higo T, Arai H
    • Organizer
      America Epilepsy Society
    • Place of Presentation
      Philadelphia, Pennsylvania Convention Center
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ictal asystoleを呈した海綿状血管腫を有するてんかん患者に対する頭蓋内電極脳波所見と病理所見2015

    • Author(s)
      中島 円, 菅野秀宣, 飯村康司, 鈴木皓晴, 肥後拓磨、新井 一
    • Organizer
      第49回日本てんかん学会
    • Place of Presentation
      長崎:長崎ブリックホール, 長崎新聞文化ホール
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
  • [Presentation] スタージウェーバー症候群96例における各診断モダリチィーの有効性と治療成績2015

    • Author(s)
      菅野秀宣、中島円、飯村康司、肥後拓磨、鈴木皓晴、新井一
    • Organizer
      第49回日本てんかん学会
    • Place of Presentation
      長崎:長崎ブリックホール, 長崎新聞文化ホール
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 皮質下出血後難治性てんかんにおける頭蓋内皮質脳波の検討2015

    • Author(s)
      鈴木皓晴、菅野秀宣、中島円、飯村康司、肥後拓磨、新井一
    • Organizer
      第49回日本てんかん学会
    • Place of Presentation
      長崎:長崎ブリックホール, 長崎新聞文化ホール
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
  • [Presentation] The predictive value of FDG-PET with 3D-SSP for patients with temporal lobe epilepsy2015

    • Author(s)
      肥後拓磨、菅野秀宣、中島円、飯村康司、鈴木皓晴、新井一
    • Organizer
      第49回日本てんかん学会
    • Place of Presentation
      長崎:長崎ブリックホール, 長崎新聞文化ホール
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
  • [Presentation] Presurgical evaluation and therapeutic outcome of 96 cases with Sturge-Weber syndrome2015

    • Author(s)
      菅野秀宣、中島円、飯村康司、肥後拓磨、鈴木皓晴、新井一
    • Organizer
      第74回日本脳神経外科学会
    • Place of Presentation
      札幌:ロイトン札幌
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] スタージウェーバー症候群に対する頭蓋内皮質脳波解析2015

    • Author(s)
      飯村康司、菅野秀宣、中島円、肥後拓磨、新井一
    • Organizer
      第74回日本脳神経外科学会
    • Place of Presentation
      札幌:ロイトン札幌
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] 3D-SSPをもちいたFDG-PETの側頭葉てんかん患者の手術予後予測における有用性について2015

    • Author(s)
      肥後拓磨、菅野秀宣、中島円、飯村康司、鈴木皓晴、新井一
    • Organizer
      第74回日本脳神経外科学会
    • Place of Presentation
      札幌:ロイトン札幌
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Glioneuronal tumorの手術は腫瘍摘出か?てんかん外科手術か?2015

    • Author(s)
      菅野秀宣、新井一
    • Organizer
      脳腫瘍の外科学会
    • Place of Presentation
      名古屋:名古屋観光ホテル
    • Year and Date
      2015-09-25
    • Related Report
      2015 Research-status Report
  • [Presentation] Inflammatory mediators’ role in epileptogenesis caused by cavernous angioma2014

    • Author(s)
      M. Nakajima, H. Sugano, T. Higo, Y Iimura, H Suzuki, Y Harada, H. Arai
    • Organizer
      America Epilepsy Society
    • Place of Presentation
      シアトル, アメリカ合衆国
    • Year and Date
      2014-12-05 – 2014-12-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 頭蓋内脳波高周波振動と局所炎症からみる海綿状血管腫近接組織のてんかん原性獲得機序の検討2014

    • Author(s)
      中島 円,菅野秀宣, 飯村康司, 肥後拓磨, 原田佳尚, 新井 一
    • Organizer
      日本脳神経外科学会第73回総会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 頭蓋内電極脳波所見と病理所見からみる海綿状血管腫周辺のてんかん原性獲得機序2014

    • Author(s)
      中島 円, 菅野秀宣, 飯村康司, 肥後拓磨, 原田佳尚, 新井 一
    • Organizer
      第48回日本てんかん学会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-02 – 2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Inflammatory mediators role in Epileptgenesis caused by Cavernous angioma.2014

    • Author(s)
      Nakajima, H. Sugano, T. Higo, Y Iimura, H Suzuki, Y Harada, H. Arai, A Furuta
    • Organizer
      10th Asian& Oceanian Epilepsy Congress
    • Place of Presentation
      Singapore
    • Year and Date
      2014-08-07 – 2014-08-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Preventive effect of Levetiracetam against the pathological changes in hippocampus of temporal lobe epilepsy model mice.2014

    • Author(s)
      T. Higo, H. Sugano, M. Nakajima, Y. Iimura, H. Arai, H. Mochizuki:
    • Organizer
      10th Asian& Oceanian Epilepsy Congress
    • Place of Presentation
      Singapore
    • Year and Date
      2014-08-07 – 2014-08-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Analysis of epileptic discharges using impanted subdural electrodes in patients with Sturge-Weber syndrome2014

    • Author(s)
      Y. Iimura, H. Sugano, M. Nakajima, T. Higo, H. Arai
    • Organizer
      10th Asian& Oceanian Epilepsy Congress
    • Place of Presentation
      Singapore
    • Year and Date
      2014-08-07 – 2014-08-10
    • Related Report
      2014 Research-status Report
  • [Presentation] 海綿状血管腫周辺の頭蓋内電極脳波所見と病理所見からみるてんかん原性獲得機序の仮説2014

    • Author(s)
      中島 円、菅野 秀宣、飯村 康司、肥後 拓磨、新井 一
    • Organizer
      日本薬物脳波学会
    • Place of Presentation
      静岡
    • Year and Date
      2014-06-13 – 2014-06-14
    • Related Report
      2014 Research-status Report
  • [Book] 新NS now 部分てんかん脳波の読み方2016

    • Author(s)
      菅野 秀宣
    • Total Pages
      10
    • Publisher
      メディカルビュー社
    • Related Report
      2016 Annual Research Report
  • [Book] 子どもの病気とその診かた2015

    • Author(s)
      菅野秀宣
    • Total Pages
      12
    • Publisher
      南山堂
    • Related Report
      2015 Research-status Report
  • [Book] 臨床てんかん学2015

    • Author(s)
      菅野秀宣
    • Total Pages
      2
    • Publisher
      医学書院
    • Related Report
      2015 Research-status Report
  • [Book] Ⅳ基本手術手技‐各論‐3, 脳神経外科診療プラクティス2014

    • Author(s)
      中島 円
    • Total Pages
      318
    • Publisher
      文光堂
    • Related Report
      2014 Research-status Report
  • [Remarks] 順天堂大学附属順天堂医院 てんかんセンター

    • URL

      http://www.juntendo.ac.jp/hospital/epilepsy/shinryo00.html#

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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