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Preconditionong treatment for the rat model of acute subdural hematoma with stemcell transplantation

Research Project

Project/Area Number 16K15768
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Emergency medicine
Research InstitutionNippon Medical School

Principal Investigator

Shoji Yokobori  日本医科大学, 医学部, 准教授 (70449271)

Co-Investigator(Kenkyū-buntansha) 増野 智彦  日本医科大学, 医学部, 講師 (00318528)
須田 智  日本医科大学, 医学部, 講師 (00366733)
山田 真吏奈  日本医科大学, 医学部, 講師 (70508621)
Research Collaborator Bullock Ross  
Gajavelli Shyam  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords幹細胞移植 / 頭部外傷 / 急性硬膜下血腫 / 減圧開頭術 / 神経再生医療 / 再生医療 / 脳低温療法 / 神経幹細胞
Outline of Final Research Achievements

The aim of this pilot study was to test feasibility using a rat ASDH decompression model with two clinically relevant transplantation methods. Two different methods, in situ stereotactic injection and hNSC-embedded matrix seating on the brain surface, were attempted. Athymic rats were randomized to uninjured or ASDH groups . Animals in injury group were subjected to ASDH, and received decompressive craniectomy and 1-week after decompression surgery were transplanted with green fluorescent protein (GFP)-transduced hNSCs using one of two approaches. Histopathological examinations at 4 and 8 weeks showed that the GFP-positive hNSCs survived in injured brain tissue. The in situ transplantation group had greater engraftment of hNSCs than matrix embedding approach. Motor function was assessed with rotarod, compared to control group (n = 10). The latency to fall from the rotarod in hNSC in situ transplanted rats was significantly higher than in control rats.

Academic Significance and Societal Importance of the Research Achievements

本研究により、神経外傷におけるヒト神経幹細胞の生着を確認できた。また、ステレオ下にIn situ に移植するのみならず、減圧開頭術後の脳表面にシートにて移植することでも生着しうることが明らかになった。神経幹細胞をInsituに移植したほうが生着の割合は高かった。どちらの細胞も4-8週生着することが明らかになり、今後のわが国の脳神経外傷の治療に向けて前進するための見地が得られた。

Report

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

    (6 results)

All 2019 2018 2016 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results)

  • [Int'l Joint Research] マイアミ大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study.2019

    • Author(s)
      Yokobori S, Sasaki K, Kanaya T, Igarashi Y, Nakae R, Onda H, Masuno T, Suda S, Sowa K, Nakajima M, Spurlock MS, Onn Chieng L, Hazel TG, Johe K, Gajavelli S, Fuse A, Bullock MR, Yokota H.
    • Journal Title

      Front Neurol

      Volume: 10 Pages: 1-7

    • DOI

      10.3389/fneur.2019.00082

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enduring Neuroprotective Effect of Subacute Neural Stem Cell Transplantation After Penetrating TBI.2019

    • Author(s)
      Kassi AAY et al.
    • Journal Title

      Front Neurol.

      Volume: 1

    • DOI

      10.3389/fneur.2018.01097

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Subdural hematoma decompression model: A model of traumatic brain injury with ischemic-reperfusional pathophysiology: A review of the literature.2018

    • Author(s)
      Yokobori S, Nakae R, Yokota H, Spurlock MS, Mondello S, Gajavelli S, Bullock RM.
    • Journal Title

      Behav Brain Res.

      Volume: 340 Pages: 23-28

    • DOI

      10.1016/j.bbr.2016.05.055

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 重症頭部外傷における神経再生医療の応用:ラット急性硬膜下血腫モデルによる検討-パイロット研究2018

    • Author(s)
      横堀 將司
    • Organizer
      第41回日本脳神経外傷学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ラット急性硬膜下血腫モデルにおける行動実験評価2016

    • Author(s)
      中井将人 朝倉隆之 横堀將司
    • Organizer
      第84回 日本医科大学医学会総会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report

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

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