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array of inflammatory mediators such as prostaglandins and leukotrienes, as
well as metabolites capable of inducing demyelination ( David, Greenhalgh,
& Lopez-Vales, 2012 ). We will discuss the identification and characterization
of their roles in SCI.
4.1. MAPK-activated protein kinase 2
This molecular target was identified from our Affymetrix microarray screen
of the contused spinal cord 7 days after injury, which corresponds to the peak
of the macrophage response ( Sroga et al., 2003 ). This screen identified al-
most 4500 differentially regulated genes, out of which 2300 were
upregulated and 2098 downregulated by 1.5-fold ( p < 0.05) in the contused
spinal cord relative to laminectomized controls ( Ghasemlou, Lopez-Vales,
et al., 2010 ). Genes of interest were identified by categorizing the up-
and downregulated genes according to function using Gene Ontology,
and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
analyses. We found that the KEGG Pathways with the greatest numbers
of genes upregulated are primarily those involved in mediating the inflam-
matory response (see Table 5.1 ). The MAPK signaling pathway was of
Table 5.1 KEGG pathways with the highest number of genes upregulated by at least
1.5-fold and p < 0.05, relative to laminectomized controls, 7 days after spinal cord
contusion injury
KEGG pathway
No. of genes
Cytokine-cytokine receptor interaction
46
Focal adhesion
42
MAPK-signaling pathway
36
Regulation of actin cytoskeleton
29
ECM-receptor interaction
28
Leukocyte transendothelial migration
27
Cell adhesion molecules
25
Hematopoietic cell lineage
23
Toll-like receptor signaling pathway
23
Jak-STAT signaling pathway
22
B-cell receptor signaling pathway
22
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