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An attempt to elucidate the pathogenesis of acute encephalopathy, in which cytokine storm is the main pathogenesis.

Research Project

Project/Area Number 17K16264
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionKumamoto Saishunso National Hospital (2018-2019)
Tottori University (2017)

Principal Investigator

Kurata Hirofumi  独立行政法人国立病院機構熊本再春荘病院(臨床研究部), 臨床研究部, 医師 (00774837)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords発熱 / サイトカイン / 痙攣 / 血液脳関門 / 急性脳症 / 高体温 / リポポリサッカライド / 脳浮腫 / 神経科学 / 脳・神経
Outline of Final Research Achievements

Acute encephalopathy (AE) is mainly reported in East Asia and, in most cases, results from pediatric viral infections. At present, Cytokine storm-induced AE is the severest among them. Here, we hypothesized that the induction of systemic inflammation using lipopolysaccharide (LPS) injection followed by hyperthermia (HT) treatment can be used to develop an animal model of AE. Postnatal eight-day-old mouse pups were injected with LPS followed by HT treatment. LPS injection followed by HT treatment increased BBB permeability in the cerebral cortex and the brains of some pups exhibited small ischemic lesions. Our results indicate that a LPS injection followed by HT treatment can produce symptoms of cytokine storm-induced AE. Thus, this mouse model can help to elucidate the pathogenetic mechanisms underlying AE.

Academic Significance and Societal Importance of the Research Achievements

急性脳症は東アジアの小児に多くみられる予後不良な疾患である。有効な治療法は開発されておらず、その原因のひとつに、汎用されるモデル動物が存在しないことがあげられる。我々は、幼若動物に細菌の構成成分を投与し、温熱処置を加えることで脳組織の浮腫を誘発し、急性脳症患者の脳組織に類似する組織所見を得たることができた。このモデル動物は、AEの病態発生メカニズムや治療法の解明に役立つと考えられる。

Report

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

    (3 results)

All 2020 2019

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Evaluation of Fluoro-Jade C staining: Specificity and application to damaged immature neuronal cells in the normal and injured mouse brain2020

    • Author(s)
      Ikenari T., Kurata H., Satoh T., Hata Y, and Mori T.
    • Journal Title

      Neuroscience

      Volume: 425 Pages: 146-156

    • DOI

      10.1016/j.neuroscience.2019.11.029

    • NAID

      120007001433

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Developing a mouse model of acute encephalopathy using low-dose lipopolysaccharide injection and hyperthermia treatment2019

    • Author(s)
      Kurata Hirofumi、Saito Kengo、Kawashima Fumiaki、Ikenari Takuya、Oguri Masayoshi、Saito Yoshiaki、Maegaki Yoshihiro、Mori Tetsuji
    • Journal Title

      Experimental Biology and Medicine

      Volume: 244 Issue: 9 Pages: 743-751

    • DOI

      10.1177/1535370219846497

    • NAID

      120006778377

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Developing mice model of acute encephalopathy using low-dose lipopolysaccharide injection and hyperthermia treatment: a simple and convenient method2019

    • Author(s)
      Hirofumi Kurata, Kengo Saito, Fumiaki Kawashima, Takuya Ikenari, Masayoshi Oguri, Yoshiaki Saito, Yoshihiro Maegaki, Tetsuji Mori
    • Organizer
      The 20th Annual Meeting of Infantile Seizure Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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