Repetitive mild traumatic brain injury in mice triggers a slowly developing cascade of long-term and persistent behavioral deficits and pathological changes
| Autor: | Reza Khazaee, Xiaoyun Xu, Marco A. M. Prado, Haojie Mao, Xingyu Liu, Flavio H. Beraldo, Mark Daley, Matthew F. Cowan, Michael J. Strong, Vania F. Prado, Timothy J. Bussey, Nicole M. Geremia, Arthur Brown, Maitray A. Patel, Zalman Brown, Karen Nygard, Lihong Lu, Ravi S. Menon, Gregory A. Dekaban, Lisa M. Saksida, Patrick McCunn, Robert Bartha, Amy L. Schranz |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Neurology Traumatic brain injury Concussion 5-Choice serial reaction time test lcsh:RC346-429 Pathology and Forensic Medicine White matter Cellular and Molecular Neuroscience Mice Magnetic resonance imaging Neuroimaging Medicine Animals Metabolomics lcsh:Neurology. Diseases of the nervous system Brain Concussion White matter pathology medicine.diagnostic_test Behavior Animal business.industry Research Diffuse axonal injury Brain medicine.disease Mice Inbred C57BL Tauopathy medicine.anatomical_structure Medical Biophysics Traumatic encephalopathy Neurology (clinical) business Neuroscience Experimental brain injury Diffusion MRI |
| Zdroj: | Acta Neuropathologica Communications Medical Biophysics Publications Brain and Mind Institute Researchers' Publications Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-27 (2021) |
| ISSN: | 2051-5960 |
| Popis: | We have previously reported long-term changes in the brains of non-concussed varsity rugby players using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional magnetic imaging (fMRI). Others have reported cognitive deficits in contact sport athletes that have not met the diagnostic criteria for concussion. These results suggest that repetitive mild traumatic brain injuries (rmTBIs) that are not severe enough to meet the diagnostic threshold for concussion, produce long-term consequences. We sought to characterize the neuroimaging, cognitive, pathological and metabolomic changes in a mouse model of rmTBI. Using a closed-skull model of mTBI that when scaled to human leads to rotational and linear accelerations far below what has been reported for sports concussion athletes, we found that 5 daily mTBIs triggered two temporally distinct types of pathological changes. First, during the first days and weeks after injury, the rmTBI produced diffuse axonal injury, a transient inflammatory response and changes in diffusion tensor imaging (DTI) that resolved with time. Second, the rmTBI led to pathological changes that were evident months after the injury including: changes in magnetic resonance spectroscopy (MRS), altered levels of synaptic proteins, behavioural deficits in attention and spatial memory, accumulations of pathologically phosphorylated tau, altered blood metabolomic profiles and white matter ultrastructural abnormalities. These results indicate that exceedingly mild rmTBI, in mice, triggers processes with pathological consequences observable months after the initial injury. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01161-2. |
| Databáze: | OpenAIRE |
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