Reduction of Cognitive and Motor Deficits After Traumatic Brain Injury in Mice Deficient in Poly(ADP-Ribose) Polymerase

• Published in: Journal of cerebral blood flow and metabolism 1999-08, Vol.19 (8), p.835-842
• Main Authors: Whalen, Michael J., Clark, Robert S. B., Dixon, C. Edward, Robichaud, Paul, Marion, Donald W., Vagni, Vincent, Graham, Steven H., Virag, Laszlo, Hasko, Gyorgy, Stachlewitz, Robert, Szabo, Csaba, Kochanek, Patrick M.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - enzymology; Brain - pathology; Brain - physiopathology; Brain Injuries - genetics; Brain Injuries - physiopathology; Brain Injuries - psychology; Cognition - physiology; Cognition Disorders - etiology; Cognition Disorders - physiopathology; Cues; Immunohistochemistry; Injuries of the nervous system and the skull. Diseases due to physical agents; Maze Learning; Medical sciences; Memory - physiology; Mice; Mice, Knockout; Motor Activity - physiology; Poly(ADP-ribose) Polymerases - deficiency; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Space Perception; Traumas. Diseases due to physical agents
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-199908000-00002

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.