Concussion or mild traumatic brain injury (mTBI) is often accompanied by long-term behavioral and neuropsychological deficits. Emerging data suggest that these deficits can be exacerbated following repeated injuries. However, despite the overwhelming prevalence of mTBI in children due to falls and sports-related activities, the effects of mTBI on white matter (WM) structure and its development in children have not been extensively examined. Moreover, the effect of repeated mTBI (rmTBI) on developing WM has not yet been studied, despite the possibility of exacerbated outcomes with repeat injuries. To address this knowledge gap, we investigated the long-term effects of single (s)mTBI and rmTBI on the WM in the pediatric brain, focusing on the anterior commissure (AC), a WM structure distant to the injury site, using diffusion tensor imaging (DTI) and immunohistochemistry (IHC). We hypothesized that smTBI and rmTBI to the developing mouse brain would lead to abnormalities in microstructural integrity and impaired oligodendrocyte (OL) development. We used a postnatal day 14 Ascl1-CreER: ccGFP mouse closed head injury (CHI) model with a bilateral repeated injury. We demonstrate that smTBI and rmTBI differentially lead to myelin-related diffusion changes in the WM and to abnormal OL development in the AC, which are accompanied by behavioral deficits 2 months after the initial injury. Our results suggest that mTBIs elicit long-term behavioral alterations and OL-associated WM dysregulation in the developing brain. These findings warrant additional research into the development of WM and OL as key components of pediatric TBI pathology and potential therapeutic targets.

中文翻译：

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反复发生的小儿脑震荡会引起长期的少突胶质细胞和白色物质微结构失调。

脑震荡或轻度创伤性脑损伤（mTBI）通常伴随长期的行为和神经心理学缺陷。新兴数据表明，这些缺陷在反复受伤后会加剧。然而，尽管由于摔倒和与运动有关的活动，儿童中mTBI的患病率很高，但尚未广泛研究mTBI对儿童白质（WM）结构及其发育的影响。此外，尽管可能会因反复受伤而加重结局，但仍未研究重复mTBI（rmTBI）对发展WM的影响。为了解决这一知识鸿沟，我们研究了单个（s）mTBI和rmTBI对小儿脑WM的长期影响，重点是前连合（AC），即距损伤部位较远的WM结构，使用扩散张量成像（DTI）和免疫组织化学（IHC）。我们假设smTBI和rmTBI进入发育中的小鼠大脑会导致微结构完整性异常和少突胶质细胞（OL）发育受损。我们使用出生后第14天的Ascl1-CreER：ccGFP小鼠双侧反复闭合性颅脑损伤（CHI）模型。我们证明，smTBI和rmTBI有区别地导致WM中髓鞘相关扩散改变和AC中OL异常发育，并伴有初始损伤后2个月的行为缺陷。我们的结果表明，mTBIs在发育中的大脑中引起长期的行为改变和与OL相关的WM失调。