Neuroproteomics pp 57-67 | Cite as
Neuroproteomic Methods in Spinal Cord Injury
- 5 Citations
- 1k Downloads
Summary
Spinal cord injury (SCI) is a major public health problem with no known effective treatment. Traumatic injury to the spinal cord initiates a host of pathophysiological events that are secondary to the initial insult leading to neuronal dysfunction and death; yet, the molecular mechanisms underlying its dysfunction are poorly understood. Furthermore, while use of imaging methods (e.g., computed tomography scans and magnetic resonance imaging) may help define injury severity and location, they do not elucidate biological mechanisms of SCI progression. The lack of comparable biomarkers for monitoring SCI makes accurate diagnosis and evaluation of SCI progression difficult. Spinal cord contusion is an extensively used SCI model in rats that best represents the etiology of SCI in humans. In this chapter, we describe a two-dimensional (2D) gel electrophoresis-based proteomic approach to investigate the injury-related differences in the proteome and phosphoproteome of spinal cord lesion epicenter at 24 h after spinal cord contusion in rats. The purpose of this study is to elucidate the mechanisms of acute spinal cord dysfunction, as well as discover novel biomarker candidates to evaluate the biological mechanisms of SCI progression and the injury severity.
Key words
Spinal cord injury Contusion 2D gel electrophoresis RatNotes
Acknowledgments
The authors would like to thank Dr. Melanie L. McEwen and Dr. Rangaswamy Rao Ravikumar for technical assistance. This work was supported by PHS grant NS46380 and an endowment from Cardinal Hill Rehabilitation Hospital.
References
- 1.Grossman, S. D., Rosenberg, L. J., and Wrathall, J. R. (2001) Temporal-spatial pattern of acute neuronal and glial loss after spinal cord contusion. Exp. Neurol. 168, 273–282.PubMedCrossRefGoogle Scholar
- 2.Springer, J. E. (2002) Apoptotic cell death following traumatic injury to the central nervous system. J. Biochem. Mol. Biol. 35, 94–105.PubMedCrossRefGoogle Scholar
- 3.Bareyre, F. M., and Schwab, M. E. (2003) Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci. 26, 555–563.PubMedCrossRefGoogle Scholar
- 4.Ahn, Y. H., Lee, G., and Kang, S. K. (2006) Molecular insights of the injured lesions of rat spinal cords: Inflammation, apoptosis, and cell survival. Biochem. Biophys. Res. Commun. 348, 560–570.PubMedCrossRefGoogle Scholar
- 5.Ling, X., and Liu, D. (2007) Temporal and spatial profiles of cell loss after spinal cord injury: Reduction by a metalloporphyrin. J. Neurosci. Res. 85, 2175–2185.PubMedCrossRefGoogle Scholar
- 6.Pearse, D. D., and Bunge, M. B. (2006) Designing cell- and gene-based regeneration strategies to repair the injured spinal cord. J. Neurotrauma 23, 438–452.PubMedCrossRefGoogle Scholar
- 7.Onifer, S. M., Rabchevsky, A. G., and Scheff, S. W. (2007) Rat models of traumatic spinal cord injury to assess motor recovery. ILAR J. 48, 385–395.PubMedCrossRefGoogle Scholar
- 8.Scheff, S. W., Rabchevsky, A. G., Fugaccia, I., Main, J. A., and Lumpp, J. E., Jr. (2003) Experimental modeling of spinal cord injury: Characterization of a force-defined injury device. J. Neurotrauma 20, 179–193.PubMedCrossRefGoogle Scholar
- 9.Cao, Q., Zhang, Y. P., Iannotti, C., DeVries, W. H., Xu, X. M., Shields, C. B., and Whittemore, S. R. (2005) Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat. Exp. Neurol. 191, S3–S16.PubMedCrossRefGoogle Scholar
- 10.Ravikumar, R., McEwen, M. L., and Springer, J. E. (2007) Post-treatment with the cyclosporin derivative, NIM811, reduced indices of cell death and increased the volume of spared tissue in the acute period following spinal cord contusion. J. Neurotrauma 24, 1618–1630.PubMedCrossRefGoogle Scholar
- 11.McEwen, M. L., Sullivan, P. G., and Springer, J. E. (2007) Pretreatment with the cyclosporin derivative, NIM811, improves the function of synaptic mitochondria following spinal cord contusion in rats. J. Neurotrauma 24, 613–624.PubMedCrossRefGoogle Scholar
- 12.Denslow, N., Miche, M. E., Temple, M. D., Hsu, C. Y., Saatman, K., and Hayes, R. L. (2003) Application of proteomics technology to the field of neurotrauma. J. Neurotrauma 20, 401–407.PubMedCrossRefGoogle Scholar
- 13.Wang, K. K., Ottens, A., Haskins, W., Liu, M. C., Kobeissy, F., Denslow, N., Chen, S., and Hayes, R. L. (2004) Proteomics studies of traumatic brain injury. Int. Rev. Neurobiol. 61, 215–240.PubMedCrossRefGoogle Scholar
- 14.Ottens, A. K., Kobeissy, F. H., Fuller, B. F., Liu, M. C., Oli, M. W., Hayes, R. L., and Wang, K. K. (2007) Novel neuroproteomic approaches to studying traumatic brain injury. Prog. Brain Res. 161, 401–418.PubMedCrossRefGoogle Scholar
- 15.Cohen, P. (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296, 613–620.PubMedCrossRefGoogle Scholar
- 16.Cohen, P. (1992) Signal integration at the level of protein kinases, protein phosphatases and their substrates. Trends Biochem. Sci. 17, 408–413.PubMedCrossRefGoogle Scholar
- 17.Gygi, S. P., Corthals, G. L., Zhang, Y., Rochon, Y., and Aebersold, R. (2000) Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc. Natl. Acad. Sci. USA 97, 9390–9395.PubMedCrossRefGoogle Scholar