title: Traumatic Brain Injury Results in Cellular, Structural and Functional Changes Resembling Motor Neuron Disease.
abstract: Traumatic brain injury (TBI) has been suggested to increase the risk of amyotrophic lateral sclerosis (ALS). However, this link remains controversial and as such, here we performed experimental moderate TBI in rats and assessed for the presence of ALS-like pathological and functional abnormalities at both 1 and 12 weeks post-injury. Serial in-vivo magnetic resonance imaging (MRI) demonstrated that rats given a TBI had progressive atrophy of the motor cortices and degeneration of the corticospinal tracts compared with sham-injured rats. Immunofluorescence analyses revealed a progressive reduction in neurons, as well as increased phosphorylated transactive response DNA-binding protein 43 (TDP-43) and cytoplasmic TDP-43, in the motor cortex of rats given a TBI. Rats given a TBI also had fewer spinal cord motor neurons, increased expression of muscle atrophy markers, and altered muscle fiber contractile properties compared with sham-injured rats at 12 weeks, but not 1 week, post-injury. All of these changes occurred in the presence of persisting motor deficits. These findings resemble some of the pathological and functional abnormalities common in ALS and support the notion that TBI can result in a progressive neurodegenerative disease process pathologically bearing similarities to a motor neuron disease.
authors: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC 3010, Australia.|Animal Imaging Facility, Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia.
authors: David K
authors: DK
authors: Wright
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia.
authors: Shijie
authors: S
authors: Liu
authors: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.
authors: Chris
authors: C
authors: van der Poel
authors: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.
authors: Stuart J
authors: SJ
authors: McDonald
authors: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.
authors: Rhys D
authors: RD
authors: Brady
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia.
authors: Lily
authors: L
authors: Taylor
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia.|Department of Histology and Embryology, Kunming Medical University, Kunming 650000, China.
authors: Li
authors: L
authors: Yang
authors: Centre for Translational Neuroscience and Mental Health, Department of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, Australia.
authors: Andrew J
authors: AJ
authors: Gardner
authors: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Roger
authors: R
authors: Ordidge
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia.
authors: Terence J
authors: TJ
authors: O'Brien
authors: Animal Imaging Facility, Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia.|Department of Electrical and Electronic Engineering, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Leigh A
authors: LA
authors: Johnston
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia.
authors: Sandy R
authors: SR
authors: Shultz
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000150:complications*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D016472:Motor Neuron Disease / Q000209:etiology / Q000503:physiopathology*; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins
keywords: MRI; TDP-43; amyotrophic lateral sclerosis; animal model; neurodegeneration