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

Danny Salah Rafati, Katja Geissler, Kathia Johnson, Geda Unabia, Claire Hulsebosch, Olivera Nesic-Taylor, J. Regino Perez-Polo

    Research output: Contribution to journalArticle

    50 Scopus citations

    Abstract

    Spinal cord injury (SCI) results in a pathophysiology characterized by multiple locomotor and sensory deficits, resulting in altered nociception and hyperalgesia. SCI triggers an early and prolonged inflammatory response, with increased interleukin-1β levels. Transient changes are observed in subunit populations of the transcription factor nuclear factor-κB (NF-κB). There were decreases in neuronal c-Rel levels and inverse increases in p65 and p50 levels. There were no changes in neuronal p52 or RelB subunits after SCI at any time point tested. Similarly, SCI had no effect on oligodendroglial levels of any NF-κB subunit. There were significant early increases in COX-2 and inducible nitric oxide synthase mRNA and protein levels after SCI. We used synthetic double-stranded "decoy" deoxyoligonucleotides containing selective NF-κB protein dimer binding consensus sequences. Decoys targeting the p65/p50 binding site on the COX-2 promoter decreased SCI-induced cell losses, NF-κB p65/p50 DNA-binding activity, and COX-2 and iNOS protein levels. NF-κB p65/p50 targeted decoys improved early locomotor recovery after moderate but not severe SCI, yet ameliorated SCI-induced hypersensitization after both moderate and severe SCI. To determine whether changes in GABA activity played a role in decreased hypersensitivity after SCI and p65/p50 targeted decoy, we counted γ-aminobutyric acid (GABA)-containing neurons in laminae 1-3. There were significantly more GABAergic neurons in the p65/p50 targeted decoy-treated group at the level of injury.

    Original languageEnglish (US)
    Pages (from-to)566-580
    Number of pages15
    JournalJournal of Neuroscience Research
    Volume86
    Issue number3
    DOIs
    StatePublished - Feb 15 2008

    Keywords

    • "Decoy"
    • COX-2
    • Deoxyoligonucleotidesspinal cord injury
    • GABAergic neuron
    • Locomotion
    • NF-κB
    • Pain

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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  • Cite this

    Rafati, D. S., Geissler, K., Johnson, K., Unabia, G., Hulsebosch, C., Nesic-Taylor, O., & Perez-Polo, J. R. (2008). Nuclear factor-κB decoy amelioration of spinal cord injury-induced inflammation and behavior outcomes. Journal of Neuroscience Research, 86(3), 566-580. https://doi.org/10.1002/jnr.21508