1. ^*Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, Pennsylvania, U.S.A.
2. ^†Department of Pediatrics, University of Pittsburgh, Pennsylvania, U.S.A.
3. ^‡Department of Neurological Surgery, University of Pittsburgh, Pennsylvania, U.S.A.
4. ^§Department of Neurology, University of Pittsburgh, Pennsylvania, U.S.A.
5. Department of the Safar Center for Resuscitation Research, University of Pittsburgh, Pennsylvania, U.S.A.
6. ^¶Department of Brain Trauma Research Center, University of Pittsburgh, Pennsylvania, U.S.A.
7. ^#Department of Pathophysiology, Medical University of Debrecen, Debrecen, Hungary
8. ^**Inotek Corporation, Beverly, Massachusetts, U.S.A.

Correspondence: Patrick M Kochanek, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260, U.S.A.

Received 14 May 1999; Accepted 6 June 1999.

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 (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, naïve 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 immunohistochemical detection of nitrated tyrosine, an indicator of peroxynitrite formation. Motor and memory performance did not differ between naïve 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 CCI were tested for motor and memory function, and contusion volume was determined by image analysis. PARP -/- mice demonstrated improved motor and memory function after CCI 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.