The pathophysiology of spinal cord injury (SCI) is characterized by multiple locomotor and sensory deficits, and chronic pain arising partly from significant cell loss at and around the injury site. Inflammatory modulators, with characteristic early increases in Interleukin 1-beta (IL-1beta) levels, are implicated as mediators of SCI-induced cell loss. IL-1beta stimulates transcription of Cyclooxygenase-2 (Cox-2) and the inducible form of Nitric Oxide Synthase (iNOS) via activation of the transcription factor nuclear factor-kappa B (NF-kappa B). Enzymes, Cox-2 and iNOS, induce cellular damage via the generation of reactive oxygen species. Double stranded deoxyoligonucleotides displaying NF-kappa B binding sequences can act as """"""""decoy oligonucleotides"""""""" by interfering with binding of NF-kappa B proteins to specific cognate gene promoters. Our goal is to design interventions that interfere with NF-kappa B-regulated transcription of Cox-2 and iNOS. We hypothesize that selective decoys will significantly decrease NF-kappa B binding to Cox-2 and iNOS promoters and Cox-2- and iNOS-induced cell death after SCI.
