• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Construction of a novel treatment paradigm based on the thermal neurobiology

Research Project

Project/Area Number 16H05438
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurosurgery
Research InstitutionYamaguchi University

Principal Investigator

NOMURA Sadahiro  山口大学, 大学院医学系研究科, 准教授 (20343296)

Co-Investigator(Kenkyū-buntansha) 柴崎 貢志  群馬大学, 大学院医学系研究科, 准教授 (20399554)
美津島 大  山口大学, 大学院医学系研究科, 教授 (70264603)
富永 真琴  大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター), 教授 (90260041)
Research Collaborator MORI Naomasa  
MORIYAMA Hiroshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsbrain cooling / epilepsy / active potential / TRPM8 / 温度生物学 / てんかん / TRP / 局所脳冷却 / Neuromodulation
Outline of Final Research Achievements

Focal brain cooling therapy for epileptic seizure and cerebral stroke has been developed. In the present study, we investigated three mechanisms of the treatment. First, brain temperature at 15℃ was effective when it was applied for focal epileptic seizure, however, not enough for inhibition of epileptic network in generalized seizure. Second, brain temperature at 15℃ reduced the frequency of neuronal depolarization, that was a mechanism to terminate seizure. Third, changing of brain function by cooling was similar to those by stimulation of TRPM8 channel and inhibition of TRPV4 channel. Namely, to modify the TRP channel function was proven to be the mechanism of the focal brain cooling on brain function. Moreover, medicines influencing TRP channel functions possibly be substituted for focal brain cooling therapy.

Academic Significance and Societal Importance of the Research Achievements

てんかんは神経細胞の異常興奮による発作を繰り返し起こす疾患、脳卒中は不可逆的な高次脳機能障害や運動機能障害を来す疾患で、いずれも難治である。てんかん焦点を冷却して発作を抑制する局所脳冷却技術と、脳卒中から脳を保護する技術が開発されている。本研究では脳温と神経ネットワークの関係、脳温と神経細胞活動の関係、脳温とTRP channelsの作用の関係を解明した。これでてんかんと脳卒中に対して脳冷却療法が有効であることが分子、細胞レベルからも証明されたことになり、冷却デバイスの開発、脳温測定機器の開発、TRP channel関連創薬等、臨床応用が推進される期待が高まった。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (21 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 10 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Limitations of Local Brain Cooling on Generalized Motor Seizures from Unknown Foci in Awake Rats2019

    • Author(s)
      He Y, Inoue T, Nomura S, Maruta Y, Kida H, Yamakawa T, Hirayama Y, Imoto H, Suzuki M.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 59 Issue: 4 Pages: 147-153

    • DOI

      10.2176/nmc.oa.2018-0112

    • NAID

      130007632870

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduction of spike generation frequency by cooling in brain slices from rats and from patients with epilepsy.2018

    • Author(s)
      Nomura S & Kida H, Hirayama Y, Imoto H, Inoue T, Moriyama H, Mitsushima D, Suzuki M.
    • Journal Title

      J Cerebr Blood F Met.

      Volume: - Issue: 11 Pages: 1-1

    • DOI

      10.1177/0271678x18795365

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design of focal brain cooling system for suppressing epileptic seizures.2017

    • Author(s)
      Hata K, Fujiwara K, Kano M, Inoue T, Nomura S, Imoto H, Suzuki M.
    • Journal Title

      Conf Proc IEEE Eng Med Biol Soc

      Volume: 2017 Pages: 283-286

    • DOI

      10.1109/embc.2017.8036817

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] Epidural focal brain cooling abolishes neocortical seizures in cats and non-human primates2017

    • Author(s)
      Inoue Takao、Fujii Masami、Kida Hiroyuki、Yamakawa Toshitaka、Maruta Yuichi、Tokiwa Tatsuji、He Yeting、Nomura Sadahiro、Owada Yuji、Yamakawa Takeshi、Suzuki Michiyasu
    • Journal Title

      Neuroscience Research

      Volume: 122 Pages: 35-44

    • DOI

      10.1016/j.neures.2017.04.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of focal brain cooling on extracellular concentration of neurotransmitters in patients with epilepsy2017

    • Author(s)
      Sadahiro Nomura, Takao Inoue, Hirochika Imoto, Eiichi Suehiro, Yuichi Maruta, Yuya Hirayama, Michiyasu Suzuki
    • Journal Title

      Epilepsia

      Volume: 58 Issue: 4 Pages: 627-634

    • DOI

      10.1111/epi.13704

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Glycine release from astrocytes via functional reversal of GlyT1.2017

    • Author(s)
      Shibasaki K, Hosoi N, Kaneko R, Ishizaki Y, Yamada K
    • Journal Title

      J. Neurochem.

      Volume: 140 Issue: 3 Pages: 395-403

    • DOI

      10.1111/jnc.13741

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Unique Distribution of Benzodiazepine Receptors in the Brain during the First Two Years of Life.2016

    • Author(s)
      Nomura S, Koizumi H, Suehiro E, Kiya H, Suzuki M
    • Journal Title

      Pediatr Neurosurg

      Volume: 51 Issue: 5 Pages: 244-248

    • DOI

      10.1159/000445903

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Brain Temperature on Cerebrovascular Autoregulation During the Acute Stage of Severe Traumatic Brain Injury.2016

    • Author(s)
      Koizumi H, Suehiro E, Fujiyama Y, Yoneda H, Ishihara H, Nomura S, Fujii M, Suzuki M
    • Journal Title

      Acta Neurochir

      Volume: 122 Pages: 193-197

    • DOI

      10.1007/978-3-319-22533-3_39

    • ISBN
      9783319225326, 9783319225333
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Motor training promotes both synaptic and intrinsic plasticity of layer II/III pyramidal neurons in the primary motor cortex.2016

    • Author(s)
      Kida H, Tsuda Y, Ito N, Yamamoto Y, Owada Y, Kamiya Y, Mitsushima D.
    • Journal Title

      Cerebral Cortex

      Volume: in press Issue: 8 Pages: 3494-507

    • DOI

      10.1093/cercor/bhw134

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation.2016

    • Author(s)
      Yoshida A, Furube E, Mannari T, Takayama Y, Kittaka H, Tominaga M, Miyata S
    • Journal Title

      Sci Rep.

      Volume: 18 Issue: 1 Pages: 26088-26088

    • DOI

      10.1038/srep26088

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳冷却によるてんかん発作抑制の機序解明2019

    • Author(s)
      野村貞宏、井本浩哉、井上貴雄、森山博史、鈴木倫保
    • Organizer
      第42回日本てんかん外科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PIT modelに対する局所脳冷却およびTRPV4 antagonistの脳保護効果2019

    • Author(s)
      森尚昌,藤山雄一,森山博史,井上貴雄,岡史朗,末廣栄一,石原秀行,野村貞宏,鈴木喜郎,富永真琴,鈴木倫保
    • Organizer
      第44回日本脳卒中学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Suppression of Generalized Onset Motor Seizure in a Rat Model by Focal Brain Cooling.2018

    • Author(s)
      Sadahiro Nomura, Yeting He, Takao Inoue, Hirochika Imoto, Hiroshi Moriyama, Takuma Nishimoto, Michiyasu Suzuki
    • Organizer
      The 46th. International Society for Pediatric Neurosurgery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラットの全般性てんかんに対する局所脳冷却療法の効果2018

    • Author(s)
      野村貞宏、井本浩哉、藤山雄一、森尚昌、鈴木倫保
    • Organizer
      一般社団法人日本脳神経外科学会 第76回学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PIT modelに対する局所脳冷却およびTRPV4 antagonistの脳保護効果2018

    • Author(s)
      森尚昌,藤山雄一,森山博史,井上貴雄,岡史朗,末廣栄一,石原秀行,野村貞宏,鈴木喜郎,富永真琴,鈴木倫保
    • Organizer
      一般社団法人日本脳神経外科学会 第76回学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TRPM8チャネル活性化による薬剤誘発性てんかん様異常脳波の抑制効果2018

    • Author(s)
      森山博史、野村貞宏、木田裕之、井上貴雄、井本浩哉、丸田雄一、藤山雄一、土師康平、美津島大、鈴木倫保
    • Organizer
      第52回日本てんかん学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Influence of a cooling compound, icilin, on penicillin G-induced epileptiform discharges in a rat model: Validation of focal cortical cooling effects by TRPM8 activation.2018

    • Author(s)
      Hiroshi Moriyama, Sadahiro Nomura, Hiroyuki Kida, Takao Inoue, Hirochika Imoto, Yuichi Maruta, Yuichi Fujiyama, Dai Mitsushima, Michiyasu Suzuki.
    • Organizer
      Society for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 難治性てんかんに対する局所脳冷却療法のための脳波・脳温・脳血流同時計測用マルチモーダルセンサの開発2017

    • Author(s)
      野村貞宏、井上貴雄、井本浩哉 、山川俊貴、丸田雄一、庭山雅嗣、平山祐哉、鈴木倫保
    • Organizer
      日本てんかん外科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effects of focal brain cooling in patients with intractable epilepsy: changes in intraoperative electrocorticogram and neurotransmitter concentrations2016

    • Author(s)
      Sadahiro Nomura, Takao Inoue, Hirochika Imoto, Yuichi Maruta, Eiichi Suehiro, Yuya Hirayama, Michiyasu Suzuki
    • Organizer
      44th Annual Meeting of the International Society for Pediatric Neurosurgery
    • Place of Presentation
      神戸ポートピアホテル(兵庫県・神戸市)
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 病態脳に対するBMI技術展開を睨んだ皮質脳波・脳表温・脳血液動態の同時計測によるマルチモーダルセンサの開発2016

    • Author(s)
      野村貞宏、井上貴雄、井本浩哉、山川俊貴、丸田雄一、庭山雅嗣、平山祐哉、鈴木倫保
    • Organizer
      一般社団法人日本脳神経外科学会 第75回学術総会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] 難治性てんかん症例における神経伝達物質濃度と、局所大脳冷却によるその変化:術中microdialysisによる検討2016

    • Author(s)
      野村貞宏、西本拓真、鈴木倫保
    • Organizer
      第44回日本小児神経外科学会
    • Place of Presentation
      つくば国際会議場(茨城県・つくば市)
    • Year and Date
      2016-06-23
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi