Inflammatory Pathways in Spinal Cord Injury - International Review of Neurobiology - page 144

modulate the inflammatory response in SCI. These approaches include:
Affymetirx gene array screening that led to the identification of MK2 that
helps orchestrate cytotoxic responses; searching for molecules identified
in other CNS conditions that led to the identification of KCa3.1 in astro-
cytes that mediate inflammation in SCI; studying molecules involved in
wound healing in tissues such as the skin that led to the identification of
the beneficial role of SLPI in SCI; and examining the role of lipolytic
enzymes belonging to the PLA 2 superfamily that led to the production of
various eicosanoids and other lipid mediators of inflammation. Our work
using small molecule inhibitors, recombinant proteins, and gene knockout
mice has provided direct evidence for the role of these molecules in SCI. In
all but one (MK2), small molecule inhibitors (KCa3.1 and PLA 2 s) or recom-
binant proteins (SLPI) were shown to be effective in reducing secondary
damage and promoting recovery of locomotor function after SCI, indicating
that these may be suitable therapeutic candidates to target for SCI in humans.
Effective treatment in humans will likely require a combination of
neuroprotection strategies such as these, combined with treatments to pro-
mote axon sprouting and regeneration.

ACKNOWLEDGMENTS
Work presented here was supported by grants from the Canadian Institutes of Health
Research (CIHR) to S. D. J. Z. is supported by a postdoctoral fellowship from the Fonds
de la recherche en sant´ du Qu´bec (FRSQ) and the CIHR Neuroinflammation
Training Program; N. G. was supported by Studentship awards from the CIHR and FRSQ.

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