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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS046136-02
Application #
6921971
Study Section
Special Emphasis Panel (ZNS1-SRB-M (01))
Program Officer
Kleitman, Naomi
Project Start
2004-05-22
Project End
2008-10-21
Budget Start
2005-05-22
Budget End
2006-05-21
Support Year
2
Fiscal Year
2005
Total Cost
$27,127
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555