Early-Life Mild Traumatic Brain Injury Alters Neurodevelopment and Behavior in Mice.

IF 1.8 Q3 CLINICAL NEUROLOGY
Neurotrauma reports Pub Date : 2025-06-30 eCollection Date: 2025-01-01 DOI:10.1089/neur.2025.0016
Rachel R Corrigan, Anna O Lanier, Emily S Dresher, Sahibjot Sran, Tracy A Bedrosian
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Abstract

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.

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早期轻度创伤性脑损伤改变小鼠神经发育和行为。
每年每10万名儿童中约有280名遭受闭合性头部损伤,其中80%以上的严重程度较轻。虽然大多数轻度受伤的儿童不需要住院,并且随着时间的推移恢复得很好,但有些儿童会经历持续的行为和认知异常,这种异常会持续到青春期。生命早期轻度创伤性脑损伤(mTBI)有可能破坏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。在这里,我们使用小鼠模型研究了早期mTBI对发育结局的影响。在出生后第7天,通过三种不同撞击强度之一的单次重量下降引起损伤。损伤后5天髓鞘碱性蛋白免疫反应性(dpi)显示,损伤导致白质明显丢失。5 dpi时iba1阳性小胶质细胞染色程度无变化;然而,在发育的这段时间,负责小胶质细胞调节的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,我们研究了先天行为和超声发声交流的发展。受伤小鼠实现发育里程碑的速度较慢,并表现出沟通改变,表明轻度损伤相关的功能缺陷。总之,这项研究为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早期轻度损伤对神经系统影响的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.40
自引率
0.00%
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审稿时长
8 weeks
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