A decoy oligonucleotide inhibiting nuclear factor-κB binding to the IgGκB consensus site reduces cerebral injury and apoptosis in neonatal hypoxic-ischemic encephalopathy

Roderic H. Fabian, J. Regino Perez-Polo, Thomas A. Kent

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    We examined the effect of treatment with intraventricular injection of a decoy oligonucleotide that binds and inhibits nuclear factor-κB on cytokine expression, ICAM-1 expression, neutrophil recruitment, apoptosis, and tissue injury in a model of neonatal hypoxic-ischemic cerebral injury with varying degrees of hypoxia. We found a reduction of interleukin-1β, tumor necrosis factor-α, soluble ICAM-1, neutrophil counts, and activity after 2 hr of hypoxia, but not with 90 min of hypoxia. By contrast, a significant reduction of apoptosis was seen in animals treated after 90 min of hypoxia but not in those treated after 2 hr of hypoxia. Overall evidence of an inflammatory response was sparse, with low levels of ICAM-1 expression and neutrophil recruitment even in the more severe hypoxic ischemic injury. It is likely that the decoy oligonucleotide affects cerebral injury and apoptosis not through suppression of downstream elements of the inflammatory response but through other mechanisms, one of which is the reduction of transcription and synthesis of cytokines, which are known to affect other responses to cellular injury.

    Original languageEnglish (US)
    Pages (from-to)1420-1426
    Number of pages7
    JournalJournal of Neuroscience Research
    Volume85
    Issue number7
    DOIs
    StatePublished - May 15 2007

    Fingerprint

    Brain Hypoxia-Ischemia
    Oligonucleotides
    Apoptosis
    Intercellular Adhesion Molecule-1
    Wounds and Injuries
    Neutrophil Infiltration
    Cytokines
    Intraventricular Injections
    Response Elements
    Interleukin-1
    Neutrophils
    Tumor Necrosis Factor-alpha
    Hypoxia

    Keywords

    • Apoptosis
    • Cerebral cortex
    • Cytokines
    • Hypoxia-ischemia
    • Immunosuppressant
    • Neonate
    • Rat

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    A decoy oligonucleotide inhibiting nuclear factor-κB binding to the IgGκB consensus site reduces cerebral injury and apoptosis in neonatal hypoxic-ischemic encephalopathy. / Fabian, Roderic H.; Perez-Polo, J. Regino; Kent, Thomas A.

    In: Journal of Neuroscience Research, Vol. 85, No. 7, 15.05.2007, p. 1420-1426.

    Research output: Contribution to journalArticle

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