A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age
Abstract Traumatic brain injury (TBI) has the highest incidence amongst the pediatric population and its mild severity represents the most frequent cases. Moderate and severe injuries as well as repetitive mild TBI result in lasting morbidity. However, whether a single mild TBI sustained during chil...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01515-y |
| _version_ | 1797863274419585024 |
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| author | Andre Obenaus Beatriz Rodriguez-Grande Jeong Bin Lee Christophe J. Dubois Marie-Line Fournier Martine Cador Stéphanie Caille Jerome Badaut |
| author_facet | Andre Obenaus Beatriz Rodriguez-Grande Jeong Bin Lee Christophe J. Dubois Marie-Line Fournier Martine Cador Stéphanie Caille Jerome Badaut |
| author_sort | Andre Obenaus |
| collection | DOAJ |
| description | Abstract Traumatic brain injury (TBI) has the highest incidence amongst the pediatric population and its mild severity represents the most frequent cases. Moderate and severe injuries as well as repetitive mild TBI result in lasting morbidity. However, whether a single mild TBI sustained during childhood can produce long-lasting modifications within the brain is still debated. We aimed to assess the consequences of a single juvenile mild TBI (jmTBI) at 12 months post-injury in a mouse model. Non-invasive diffusion tensor imaging (DTI) revealed significant microstructural alterations in the hippocampus and the in the substantia innominata/nucleus basalis (SI/NB), structures known to be involved in spatial learning and memory. DTI changes paralled neuronal loss, increased astrocytic AQP4 and microglial activation in the hippocampus. In contrast, decreased astrocytic AQP4 expression and microglia activation were observed in SI/NB. Spatial learning and memory were impaired and correlated with alterations in DTI-derived derived fractional ansiotropy (FA) and axial diffusivity (AD). This study found that a single juvenile mild TBI leads to significant region-specific DTI microstructural alterations, distant from the site of impact, that correlated with cognitive discriminative novel object testing and spatial memory impairments at 12 months after a single concussive injury. Our findings suggest that exposure to jmTBI leads to a chronic abnormality, which confirms the need for continued monitoring of symptoms and the development of long-term treatment strategies to intervene in children with concussions. |
| first_indexed | 2024-04-09T22:32:55Z |
| format | Article |
| id | doaj.art-7e142d6a10964dbd93102df8b9824056 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-09T22:32:55Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-7e142d6a10964dbd93102df8b98240562023-03-22T12:39:23ZengBMCActa Neuropathologica Communications2051-59602023-03-0111112010.1186/s40478-023-01515-yA single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle ageAndre Obenaus0Beatriz Rodriguez-Grande1Jeong Bin Lee2Christophe J. Dubois3Marie-Line Fournier4Martine Cador5Stéphanie Caille6Jerome Badaut7Department of Pediatrics, University of CaliforniaCNRS, EPHE, INCIA UMR5287, University of BordeauxDepartment of Basic Sciences, Loma Linda University School of MedicineCNRS UMR 5536 RMSB, University of BordeauxCNRS, EPHE, INCIA UMR5287, University of BordeauxCNRS, EPHE, INCIA UMR5287, University of BordeauxCNRS, EPHE, INCIA UMR5287, University of BordeauxDepartment of Basic Sciences, Loma Linda University School of MedicineAbstract Traumatic brain injury (TBI) has the highest incidence amongst the pediatric population and its mild severity represents the most frequent cases. Moderate and severe injuries as well as repetitive mild TBI result in lasting morbidity. However, whether a single mild TBI sustained during childhood can produce long-lasting modifications within the brain is still debated. We aimed to assess the consequences of a single juvenile mild TBI (jmTBI) at 12 months post-injury in a mouse model. Non-invasive diffusion tensor imaging (DTI) revealed significant microstructural alterations in the hippocampus and the in the substantia innominata/nucleus basalis (SI/NB), structures known to be involved in spatial learning and memory. DTI changes paralled neuronal loss, increased astrocytic AQP4 and microglial activation in the hippocampus. In contrast, decreased astrocytic AQP4 expression and microglia activation were observed in SI/NB. Spatial learning and memory were impaired and correlated with alterations in DTI-derived derived fractional ansiotropy (FA) and axial diffusivity (AD). This study found that a single juvenile mild TBI leads to significant region-specific DTI microstructural alterations, distant from the site of impact, that correlated with cognitive discriminative novel object testing and spatial memory impairments at 12 months after a single concussive injury. Our findings suggest that exposure to jmTBI leads to a chronic abnormality, which confirms the need for continued monitoring of symptoms and the development of long-term treatment strategies to intervene in children with concussions.https://doi.org/10.1186/s40478-023-01515-yMild TBIBasal forebrain/cholinergic systemHippocampusAQP4DTIMemory |
| spellingShingle | Andre Obenaus Beatriz Rodriguez-Grande Jeong Bin Lee Christophe J. Dubois Marie-Line Fournier Martine Cador Stéphanie Caille Jerome Badaut A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age Acta Neuropathologica Communications Mild TBI Basal forebrain/cholinergic system Hippocampus AQP4 DTI Memory |
| title | A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age |
| title_full | A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age |
| title_fullStr | A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age |
| title_full_unstemmed | A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age |
| title_short | A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age |
| title_sort | single mild juvenile tbi in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age |
| topic | Mild TBI Basal forebrain/cholinergic system Hippocampus AQP4 DTI Memory |
| url | https://doi.org/10.1186/s40478-023-01515-y |
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