Corrigan Rachel R, Lanier Anna O, Dresher Emily S, Sran Sahibjot, Bedrosian Tracy A
Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Neurotrauma Rep. 2025 Jun 30;6(1):465-479. doi: 10.1089/neur.2025.0016. eCollection 2025.
Approximately 280 children per 100,000 experience closed-head injuries each year, with over 80% being mild in severity. While most children with mild injuries do not require admission to a hospital and recover well over time, some children experience persistent behavioral and cognitive abnormalities that continue into adolescence. Mild traumatic brain injury (mTBI) during early life has potential to disrupt critical developmental processes and lead to long-term consequences; however, the mechanistic underpinnings of mTBI's effects on brain development remain understudied. Here, we investigated the effects of early-life mTBI on developmental outcomes using a mouse model. Injury was induced on post-natal day 7 by a single weight drop of one of three different impact intensities. Injury resulted in significant white matter loss as measured by myelin basic protein immunoreactivity at 5 days post injury (dpi). There was no change in the extent of Iba1-positive microglial staining at 5 dpi; however, there was increased expression of complement signaling proteins responsible for microglial-regulated synaptic pruning during this time in development. To assess the neurological consequences of mTBI, we examined the development of innate behaviors and ultrasonic vocalization communication. Injured mice were slower to achieve developmental milestones and exhibited altered communication, indicating functional deficits associated with mild injury. Altogether, this study provides evidence for neurodevelopmental consequences of mTBI and demonstrates lasting behavioral effects, suggesting further investigation of mechanisms contributing to neurological effects of mild injury in early life is warranted.
每年每10万名儿童中约有280名经历闭合性头部损伤，其中超过80%为轻度损伤。虽然大多数轻度损伤的儿童不需要住院治疗，且随着时间的推移恢复良好，但一些儿童会出现持续的行为和认知异常，并持续到青春期。生命早期的轻度创伤性脑损伤（mTBI）有可能扰乱关键的发育过程并导致长期后果；然而，mTBI对大脑发育影响的机制基础仍未得到充分研究。在此，我们使用小鼠模型研究了生命早期mTBI对发育结果的影响。在出生后第7天，通过三种不同冲击强度之一的单次重物下落诱导损伤。损伤后5天（dpi），通过髓鞘碱性蛋白免疫反应性测量，损伤导致显著的白质损失。在5 dpi时，Iba1阳性小胶质细胞染色范围没有变化；然而，在这个发育阶段，负责小胶质细胞调节突触修剪的补体信号蛋白的表达增加。为了评估mTBI的神经学后果，我们检查了先天行为和超声波发声交流的发育情况。受伤小鼠达到发育里程碑的速度较慢，并且表现出发声改变，表明与轻度损伤相关的功能缺陷。总之，本研究为mTBI的神经发育后果提供了证据，并证明了持久的行为影响，表明有必要进一步研究导致生命早期轻度损伤神经学影响的机制。
