title: Microwave & Magnetic (M2) Proteomics of a Mouse Model of Mild Traumatic Brain Injury.
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 & 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 M2proteomics 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.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Evans
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK, USA ; Oklahoma City VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.affiliation: Pediatric Biochemistry Laboratory, Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Purkar
authors.affiliation: Pediatric Biochemistry Laboratory, Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: Swetha
authors.initials: S
authors.lastname: Mahesula
authors.affiliation: Department of Epidemiology & Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: J Al
authors.initials: JA
authors.lastname: Gelfond
authors.affiliation: South Texas Veterans Health Care System, San Antonio, Texas, USA, Department of Rehabilitation Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Marian
authors.initials: M
authors.lastname: Sabia
authors.affiliation: South Texas Veterans Health Care System, San Antonio, Texas, USA, Department of Rehabilitation Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Qi
authors.affiliation: Research Imaging Institute, Barshop Institute and Department of Cellular & Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, USA.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Lin
authors.affiliation: Polytrauma Rehabilitation Center, South Texas Veterans Health Care System, San Antonio, Texas, USA, Department of Rehabilitation Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Jaramillo
authors.affiliation: Pediatric Biochemistry Laboratory, Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Haskins
keywords: MAG; MBP; biomarkers; central nervous system-specific protein; magnetic; microwave; mild traumatic brain injury; motor impairment; proteins; proteomics