Neutrophil extracellular traps contribute multiple organ failure after traumatic brain injury

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K17324
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Kyoto University
• Principal Investigator: Kawai Chihiro 京都大学, 医学研究科, 助教 (40894754)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 法医病理学 / 頭部外傷

Outline of Final Research Achievements

The mechanism through which traumatic brain injury (TBI) results in multiple organ injuries remains unclear. In this study, we used mouse models to investigate the pathological changes that occur in various organs following life-threatening TBI, with a focus on the role of damage-associated molecular patterns (DAMPs) such as neutrophil extracellular traps (NETs) and high-mobility group box 1 (HMGB1) in peripheral organs. Our findings suggest that during the acute phase following TBI, inflammation spreads to peripheral organs, while the disruption of neuromodulatory mechanisms contributes to organ damage in the subacute phase. Although NETs were observed in the brain-injured area, no systemic effects were detected. Conversely, HMGB1 displayed opposing functions in the central and peripheral regions, exacerbating inflammation in the brain-injured area while acting as an inflammation suppressor in other organs during the acute phase.

Free Research Field

法医病理学

Academic Significance and Societal Importance of the Research Achievements

近年、HMGB1は頭部外傷に対する新たな治療標的として着目されている。しかしながら、本研究により外傷性脳損傷において、HMGB1は相反する機能を有していることが示唆された。新たな治療法の確立には、損傷局所に留まらず、全身の詳細な評価が必要であることを再認識させる。また、HMGB1は未だ機序が不明確な脳損傷誘導性末梢免疫抑制機構に寄与している可能性があり、今後はマクロファージを起点とした外傷時の末梢免疫制御機構を解明し、末梢臓器への影響から見た新たな予防・治療法の確立に貢献したい。