Repeated Pediatric Concussions Evoke Long-Term Oligodendrocyte and White Matter Microstructural Dysregulation Distant from the Injury
| Autor: | Jeff Dunn, Jeong Bin Lee, Andrea C. Pardo, Andre Obenaus, Mary Hamer, Yaritxa Gamboa, Bethann M. Affeldt |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Traumatic brain injury Mice Transgenic Anterior commissure Time White matter OLIG2 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience 030225 pediatrics Concussion medicine Animals Brain Concussion Myelin Sheath business.industry Neuropsychology medicine.disease White Matter Disease Models Animal Oligodendroglia Diffusion Tensor Imaging medicine.anatomical_structure Neurology Brain Injuries Closed head injury Female business Neuroscience 030217 neurology & neurosurgery Diffusion MRI |
| Zdroj: | Developmental Neuroscience. 40:358-375 |
| ISSN: | 1421-9859 0378-5866 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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