Beneficial effects of PJ34 and INO-1001, two novel water-soluble poly(ADP-ribose) polymerase inhibitors, on the consequences of traumatic brain injury in rat

Valérie C. Besson, Zsuzsanna Zsengellér, Michel Plotkine, Csaba Szabó, Catherine Marchand-Verrecchia

    Research output: Contribution to journalArticle

    37 Scopus citations

    Abstract

    Traumatic brain injury produces peroxynitrite, a powerful oxidant which triggers DNA strand breaks, leading to the activation of poly(ADP-ribose) polymerase-1 (PARP-1). We previously demonstrated that 3-aminobenzamide, a PARP inhibitor, is neuroprotective in a model of traumatic brain injury induced by fluid percussion in rat, suggesting that PARP-1 could be a therapeutic target. In order to confirm this hypothesis, we investigated the effects of PJ34 and INO-1001, two PARP inhibitors from structural classes other than benzamide, on the post-traumatic consequences. Pre- and post-treatments with PJ34 (30 mg/kg/day) and INO-1001 (10 mg/kg/day) decrease the neurological deficit at 3 days post-injury and this deficit is still reduced at 7 days. These neurological recovery-promoting effects are associated with the inhibition of PARP-1 activation caused by trauma, as demonstrated by abolishment of immunostaining of poly(ADP-ribose). Thus, the present work strengthens strongly the concept that PARP-1 inhibition may be a suitable approach for the treatment of brain trauma.

    Original languageEnglish (US)
    Pages (from-to)149-156
    Number of pages8
    JournalBrain Research
    Volume1041
    Issue number2
    DOIs
    StatePublished - Apr 18 2005

    Keywords

    • Inhibitors
    • Neurological deficit
    • Neuroprotection
    • Poly(ADP-ribose) polymerase
    • Rat
    • Traumatic brain injury

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Molecular Biology
    • Clinical Neurology
    • Developmental Biology

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