Repetitive mild traumatic brain injury in mice triggers a slowly developing cascade of long-term and persistent behavioral deficits and pathological changes.

Autor: Xu X; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Cowan M; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Beraldo F; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Schranz A; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., McCunn P; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Geremia N; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Brown Z; Department of Computer Science, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Patel M; Department of Computer Science, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Nygard KL; The Biotron Experimental Climate Change Research Centre, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Khazaee R; The Biotron Experimental Climate Change Research Centre, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Lu L; Department of Mechanical and Materials Engineering, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Liu X; Department of Mechanical and Materials Engineering, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Strong MJ; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, N6A 5B7, Canada., Dekaban GA; Molecular Medicine Research Laboratories, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Menon R; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Centre for Functional and Metabolic Mapping, Robarts Research Institute, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Bartha R; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Centre for Functional and Metabolic Mapping, Robarts Research Institute, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Daley M; Department of Computer Science, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; The Vector Institute for Artificial Intelligence, 661 University Ave Suite 710, Toronto, Canada., Mao H; Department of Mechanical and Materials Engineering, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Prado V; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Anatomy and Cell Biology, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Prado MAM; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Anatomy and Cell Biology, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Saksida L; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Bussey T; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Brown A; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada. abrown@robarts.ca.; Department of Anatomy and Cell Biology, The University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada. abrown@robarts.ca.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2021 Apr 06; Vol. 9 (1), pp. 60. Date of Electronic Publication: 2021 Apr 06.
DOI: 10.1186/s40478-021-01161-2
Abstrakt: 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.
Databáze: MEDLINE
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