The effect of mild traumatic brain injury on peripheral nervous system pathology in wild-type mice and the G93A mutant mouse model of motor neuron disease.
Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. Mild-TBI did not alter the lifespan of G93A mice or age of onset; however, rotarod performance was impaired in G93A verses wild-type mice. Grip strength was reduced only in G93A mice after mild-TBI. Increased electromyography (EMG) abnormalities and markers of denervation (AchR, Runx1) indicate that mild-TBI may result in peripheral effects that are exaggerated in G93A mice. Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice.
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: EvansTM@uthscsa.edu.
T M
TM
Evans
Polytrauma Rehabilitation Center, San Antonio, TX, USA; South Texas Veterans Health Care System, San Antonio, TX, USA; Department of Rehabilitation Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: jaramilloc3@uthscsa.edu.
C A
CA
Jaramillo
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USA. Electronic address: Kavithalakshmi-Sataranatarajan@omrf.org.
K
K
Sataranatarajan
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: wattsl@uthscsa.edu.
L
L
Watts
South Texas Veterans Health Care System, San Antonio, TX, USA. Electronic address: sabia@uthscsa.edu.
M
M
Sabia
South Texas Veterans Health Care System, San Antonio, TX, USA. Electronic address: Qi@uthscsa.edu.
W
W
Qi
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USA. Electronic address: holly-vanremmen@omrf.org.
H
H
Van Remmen
D000367:Age Factors; D000818:Animals; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000235:genetics* / Q000503:physiopathology*; D053580:Muscle Strength / Q000235:genetics; D009154:Mutation / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D017933:Peripheral Nervous System / Q000473:pathology*; D011930:Reaction Time / Q000235:genetics; D011950:Receptors, Cholinergic / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D005904:Glial Fibrillary Acidic Protein; D017570:MyoD Protein; D009687:Nuclear Proteins; D011950:Receptors, Cholinergic; D013482:Superoxide Dismutase; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins; C109415:SOD1 G93A protein
TBI; amyotrophic lateral sclerosis; mouse model; oxidative stress; spinal cord