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

Poly(ADP-ribose) polymerase (PARP), or poly (ADP-ribose) synthetase, is a n uclear enzyme that consumes NAD when activated by DNA damage. The role of P ARP in the pathogenesis of traumatic brain injury (TBI) is unknown. Using a controlled cortical impact (CCI) model of TBI and mice deficient in PARP, the authors studied the effect of PARP on functional and histologic outcome after CCI using two protocols. In protocol 1, naive mice (n = 7 +/+, n = 6 -/-) were evaluated for motor and memory acquisition before CCI. Mice were then subjected to severe CCI and killed at 24 hours for immunohistochemica l 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, suggestin g that peroxynitrite is produced in contused brain. In protocol 2, mice (PA RP +/+, n = 8; PARP -/-, n = 10) subjected to CCI were tested for motor and memory function, and contusion volume was determined by image analysis. PA RP -/- mice demonstrated improved motor and memory function after CCI versu s PARP +/+ mice (P < 0.05). However, contusion volume was not different bet ween groups. The results suggest a detrimental effect of PARP on functional outcome after TBI.