Title

Nuclear factor-κB decoy amelioration of spinal cord injury-induced inflammation and behavior outcomes

Document Type

Article

Department

Brain and Mind Institute

Abstract

Spinal cord injury (SCI) results in a pathophysiologycharacterized by multiple locomotor and sensory defi-cits, resulting in altered nociception and hyperalgesia.SCI triggers an early and prolonged inflammatoryresponse, with increased interleukin-1blevels. Transientchanges are observed in subunit populations of thetranscription factor nuclear factor-jB (NF-jB). Therewere decreases in neuronal c-Rel levels and inverseincreases in p65 and p50 levels. There were nochanges in neuronal p52 or RelB subunits after SCI atany time point tested. Similarly, SCI had no effect onoligodendroglial levels of any NF-jB subunit. Therewere significant early increases in COX-2 and induciblenitric oxide synthase mRNA and protein levels afterSCI. We used synthetic double-stranded ‘‘decoy’’ deox-yoligonucleotides containing selective NF-jB proteindimer binding consensus sequences. Decoys targetingthe p65/p50 binding site on the COX-2 promoterdecreased SCI-induced cell losses, NF-jB p65/p50DNA-binding activity, and COX-2 and iNOS protein lev-els. NF-jB p65/p50 targeted decoys improved earlylocomotor recovery after moderate but not severe SCI,yet ameliorated SCI-induced hypersensitization afterboth moderate and severe SCI. To determine whetherchanges in GABA activity played a role in decreasedhypersensitivity after SCI and p65/p50 targeted decoy,we countedg-aminobutyric acid (GABA)-containingneurons in laminae 1–3. There were significantly moreGABAergic neurons in the p65/p50 targeted decoy-treated group at the level of injury.

Publication

2008

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