Microwave and magnetic (M2) proteomics of a mouse model of mild traumatic brain injury

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 120days 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 30days 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 30days 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.

Original languageEnglish
Pages (from-to)10-21
Number of pages12
JournalTranslational Proteomics
Volume3
Issue number1
DOIs
StatePublished - Jun 2014

Bibliographical note

Funding Information:
We acknowledge the RCMI and RTRN grants from the National Institute on Minority Health and Health Disparities ( G12MD007591 and U54MD008149 , respectively) for funding (Haskins WE). This research was funded in part by an independent National Research Service Award, National Institute for Neurological Diseases and Stroke ( 1F31NS080508-01 ; Evans TM) and the Hartford Foundation/American Federation for Aging Research Scholars in Geriatric Medicine Program (Jaramillo CA). We would also like to acknowledge the support of the Sam and Ann Barshop institute for Longevity and Aging Studies. Lastly, we thank the dedicated patients, physicians and researchers in the TBI community for their strong support of protein biomarker research for TBI. The authors have no conflicts of interest to report.

Keywords

  • Biomarkers
  • Central nervous system-specific protein
  • MAG
  • MBP
  • Magnetic
  • Microwave
  • Mild traumatic brain injury
  • Motor impairment
  • Proteins
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry

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