Research for blast induced traumatic brain injury

• Project/Area Number: 17K17050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Osaka University
• Principal Investigator: Matsuura Hiroshi 大阪大学, 医学部附属病院, 医員 (10791709)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 爆発 / 慢性外傷性脳症 / mild TBI / 衝撃波 / 頭部爆傷 / 行動異常 / 衝撃波外傷 / blast injury / 頭部外傷 / shock wave / depression like behavior / 衝撃波頭部外傷モデル / 免疫染色iba1 / 体重変化

Outline of Final Research Achievements

This study aimed to establish a rat model of behavioral abnormality caused by blast-induced mTBI and detect new findings.We used a bench-top blast wave generator. The blast wave was directed at the head of male Wistar rats. Peak shock wave pressure was 646.2 ± 70.3 kPa.After blast injury, mTBI rats did not show the findings of brain hemorrhage macroscopically and on hematoxylin-eosin-stained frozen sections. Behavioral experiments revealed short-term memory impairment at 2 weeks and depression-like behavior at 2 and 6 weeks. Diffusion-weighted ex vivo MRI showed high-intensity areas in layers of the bilateral hippocampus. Immunohistochemical analysis revealed accumulation of reactive microglia and GFAP-positive astrocytes in the same region and loss of NeuN-positive neurons in the hippocampal pyramidal cell layer.This model can reflect the pathophysiology of blast-induced mTBI and could potentially be used to develop therapeutic interventions in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究は頭部局所の軽症爆傷モデルであり、ヒトで問題となっている急性期以降の症状を表現しているモデルを作成できた。そのモデルにおいて超高磁場MRIや免疫組織学的変化を捉えることができ、慢性的な炎症性変化が病態を形成していることが示唆され、今後のさらなる病態の解明や治療介入を試みるよいモデルになりうる。また、軽症頭部爆傷で生じる症状は、負傷者がさらに多い脳震盪など軽症頭部外傷でも見られ、類似点が多いため、本研究の成果は応用できる可能性がある。

Research Products

• [Journal Article] Original experimental rat model of blast-induced mild traumatic brain injury: a pilot study. (2021)
  • Author(s): Matsuura H, Ohnishi M, Yoshioka Y, Togami Y, Hosomi S, Umemura Y, Ebihara T, Shimizu K, Ogura H, Shimazu T.
  • Journal Title: Brain Injury Volume: 16 Issue: 3 Pages: 1-14
  • DOI: 10.1080/02699052.2020.1861653
  • Peer Reviewed / Open Access
• [Presentation] Primary blast-induced mild traumatic brain injury shows changes in MRI and immunohistology in a rat model of blast-induced behavioral abnormality (2019)
  • Author(s): 松浦裕司
  • Organizer: 78th Annual Meeting of AAST & Clinical Congress of Acute Care Surgery.
  • Int'l Joint Research
• [Presentation] Primary blast-induced mild traumatic brain injury shows changes in MRI and immunohistology in a rat model of blast-induced behavioral abnormality (2019)
  • Author(s): 松浦裕司
  • Organizer: International foram of blast injury countermeasure
  • Int'l Joint Research
• [Presentation] 当教室での軽症頭部爆傷の研究 (2019)
  • Author(s): 松浦裕司
  • Organizer: 日本爆傷フォーラム
  • Invited
• [Presentation] ラット頭部衝撃波外傷モデルにおける呼吸・循環動態への影響 (2018)
  • Author(s): 松浦裕司
  • Organizer: 日本救急医学会総会
• [Presentation] A NOVEL LABORATORY RAT MODEL OF FOCUSED BLAST WAVE-INDUCED MILD TRAUMATIC BRAIN INJURY (2018)
  • Author(s): 松浦裕司
  • Organizer: American Association Surgery for Trauma
  • Int'l Joint Research
• [Presentation] A NOVEL LABORATORY RAT MODEL OF FOCUSED BLAST WAVE-INDUCED MILD TRAUMATIC BRAIN INJURY (2018)
  • Author(s): 松浦裕司
  • Organizer: Japan USA forum of blast injury
• [Remarks] Shock Wave Trauma Research
  • URL: https://www.ingentaconnect.com/content/sil/impact/2019/00002019/00000003/art00029