期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 39, 页码 8562-8576出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3316-04.2004
关键词
spinal cord; microarray; gene expression; transcriptional profiling; injury; extracellular matrix; inflammation; T cells; degeneration; regeneration; contusion; magnetic resonance
资金
- NCRR NIH HHS [P41 RR16105, P41 RR016105] Funding Source: Medline
- NINDS NIH HHS [R01 NS42075, P01-NS36302, R01 NS042075, P01 NS036302] Funding Source: Medline
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.
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