 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, September 29, 2004, 24(39):8562-8576; doi:10.1523/JNEUROSCI.3316-04.2004
Previous Article | Next Article
Development/Plasticity/Repair
Patterns of Gene Expression Reveal a Temporally Orchestrated Wound Healing Response in the Injured Spinal Cord
Margaret J. Velardo,1,4,5,6 Corinna Burger,2,4,5,6 Philip R. Williams,1,4 Henry V. Baker,2,4,5,6 M. Cecilia López,2,5,6 Thomas H. Mareci,3,4 Todd E. White,1,4 Nicholas Muzyczka,2,4,5,6 andPaul J. Reier1,4,5 1Department of Neuroscience, 2Department of Molecular Genetics and Microbiology, 3Department of Biochemistry and Molecular Biology, 4McKnight Brain Institute, 5Powell Gene Therapy Center, and 6UF Genetics Institute, College of Medicine, University of Florida, Gainesville, Florida 32610
Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.
Key words: spinal cord; microarray; gene expression; transcriptional profiling; injury; extracellular matrix; inflammation; T cells; degeneration; regeneration; contusion; magnetic resonance
Received Aug 12, 2004; revised August 16, 2004; accepted August 16, 2004.
This article has been cited by other articles:
N. Komori, N. Takemori, H. K. Kim, A. Singh, S.-H. Hwang, R. D. Foreman, K. Chung, J. M. Chung, and H. Matsumoto
Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury
Physiol Genomics, April 24, 2007; 29(2): 215 - 230.
[Abstract] [Full Text] [PDF]
Y. Ohori, S.-i. Yamamoto, M. Nagao, M. Sugimori, N. Yamamoto, K. Nakamura, and M. Nakafuku
Growth Factor Treatment and Genetic Manipulation Stimulate Neurogenesis and Oligodendrogenesis by Endogenous Neural Progenitors in the Injured Adult Spinal Cord.
J. Neurosci., November 15, 2006; 26(46): 11948 - 11960.
[Abstract] [Full Text] [PDF]
A. De Biase, S. M. Knoblach, S. Di Giovanni, C. Fan, A. Molon, E. P. Hoffman, and A. I. Faden
Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity
Physiol Genomics, August 11, 2005; 22(3): 368 - 381.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|