The neuroprotective effect of recombinat thrombomoduline on the rodent model of heatstroke.

2019 Fiscal Year Final Research Report

• Project/Area Number: 15K10993
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Showa University
• Principal Investigator: Miyamoto Kazuyuki 昭和大学, 医学部, 講師 (80555087)
• Co-Investigator(Kenkyū-buntansha): 大滝 博和 昭和大学, 医学部, 准教授 (20349062)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Keywords: 熱中症 / 協調運動障害 / Prukinje細胞 / 小脳 / 遺伝子組み換えトロンボモジュリン / 神経炎症

Outline of Final Research Achievements

Coordination deficit post heat exposure (HE) is one of the problem. Thought, it is well understood the mechanism of coordination deficit post heat exposure. In our study, we established the mice heatstroke model to evaluate the middle and long term neurodeficit. In our result, coordination deficit appeared 1 weeks post HE and worsen 3 weeks post HE.
Recombinant thrombomodulin (rTM) was clinically used for DIC. Recently, it is reported rTM also has the anti-inflammatory effect. Coordination deficit was siginificantly improved in rTM post 3 weeks HE. Moreover, rTM significantly decrease TNF-α at cerebellum 1week post HE. These results suggest that administration of rTm suppresses the inflammatory cytokine 1 week post HE and improves the neurological function. It may contribute to early rising after heatstroke in clinical setting.

Free Research Field

救急医学

Academic Significance and Societal Importance of the Research Achievements

急性期の熱中症の病態を解明するためのマウス熱中症モデルはいくつか報告されているが中長期(1-3ヶ月)について検討をおこなった報告はない。本研究では熱中症後1-3週で協調運動障害を呈するモデルを確立した。今後の熱中症後の神経傷害を解明する際に役立ち、熱中症後の神経傷害解明につながる社会的意義があると考える。
また、遺伝子組み換えトロンボモジュリン(rTM)投与は熱中症後の脳内の炎症性サイトカインを抑制することで熱中症後3週目に協調運動障害を改善した。rTMはすでに臨床で用いられており、熱中症(Ⅲ度)へのrTM投与は離床を早め、社会復帰に繋がる可能性があると考える。