Year: 2014
Type: article
Abstract: Short-term increases in oxidative stress and decreases in motor function, including debilitating effects on balance and motor control, can occur following primary mild traumatic brain injuries (mTBI). However, the long-term effects on motor unit impairment and integrity as well as the molecular mechanisms underlying secondary injuries are poorly understood. We hypothesized that changes in central nervous system-specific protein (CSP) expression might correlate to these long-term effects. To test our hypothesis, we longitudinally assessed a closed-skull mTBI mouse model, vs. sham control, at 1, 7, 30, and 120 days post-injury. Motor impairment was determined by rotarod and grip strength performance measures, while motor unit integrity was determined using electromyography. Relative protein expression was determined by microwave and magnetic (M2) proteomics of ipsilateral brain tissue, as previously described. Isoprostane measurements were performed to confirm a primary oxidative stress response. Decoding the relative expression of 476 ± 56 top-ranked proteins for each specimen revealed statistically significant changes in the expression of two well-known CSPs at 1, 7 and 30 days post-injury: P < 0.001 for myelin basic protein (MBP) and p < 0.05 for myelin associated glycoprotein (MAG). This was confirmed by Western blot. Moreover, MAG, αII-spectrin (SPNA2) and neurofilament light (NEFL) expression at 30 days post-injury were directly related to grip strength (p < 0.05). While higher-powered studies of larger cohorts merit further investigation, this study supports the proof-of-concept that M2 proteomics is a rapid method to quantify putative protein biomarkers and therapeutic targets of mTBI and suggests the feasibility of CSP expression correlations to long-term effects on motor impairment.
Source: Translational Proteomics
Authors: Teresa M. Evans, Holly Van Remmen, Anjali Purkar, Swetha Mahesula, J.A.L. Gelfond, Marian Sabia, Wenbo Qi, Ai-Ling Lin, Carlos A. Jaramillo, William E. Haskins
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $1,950
Funders: U.S. Department of Veterans Affairs, American Federation for Aging Research, Hartford Foundation for Public Giving, National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: RCMI Translational Research Network (RTRN), G2237892612, Institute for Integration of Medicine & Science: A Partnership to Improve Health, G4033523274, G4037572796, RCMI Center for Interdiscplinary Health Research CIHR, Neuroimaging Assessments of Brain Integrity in Aging Mice, The mechanism linking traumatic brain injury to amyotrophic lateral sclerosis, Institute for Integration of Medicine & Science: A Partnership to Improve Health
OpenAlex ID: W2034983095
