Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase

Michael J. Whalen, Robert S.B. Clark, C. Edward Dixon, Paul Robichaud, Donald W. Marion, Vincent Vagni, Steven H. Graham, Laszlo Virag, Gyorgy Hasko, Robert Stachlewitz, Csaba Szabo, Patrick M. Kochanek

    Research output: Contribution to journalArticlepeer-review

    133 Scopus citations

    Abstract

    Poly(ADP-ribose) polymerase (PARP), or poly(ADP-ribose) synthetase, is a nuclear enzyme that consumes NAD when activated by DNA damage. The role of PARP in the pathogenesis of traumatic brain injury (TBI) is unknown. Using a controlled cortical impact (CCl) model of TBI and mice deficient in PARP, the authors studied the effect of PARP on functional and histologic outcome after CCl using two protocols. In protocol 1, naive mice (n = 7 +/+, n = 6 -/-) were evaluated for motor and memory acquisition before CCl. Mice were then subjected to severe CCl and killed at 24 hours for immunohistochemical detection of nitrated tyrosine, an indicator of peroxynitrite formation. Motor and memory performance did not differ between naive PARP +/+ and -/- mice. Both groups showed nitrotyrosine staining in the contusion, suggesting that peroxynitrite is produced in contused brain. In protocol 2, mice (PARP +/+, n = 8; PARP -/-, n = 10) subjected to CCl were tested for motor and memory function, and contusion volume was determined by image analysis. PARP -/- mice demonstrated improved motor and memory function after CCl versus PARP +/+ mice (P < 0.05). However, contusion volume was not different between groups. The results suggest a detrimental effect of PARP on functional outcome after TBI.

    Original languageEnglish (US)
    Pages (from-to)835-842
    Number of pages8
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume19
    Issue number8
    DOIs
    StatePublished - 1999

    Keywords

    • Brain injury
    • Controlled cortical impact
    • Mice
    • Poly(ADP-ribose) polymerase

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine

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