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 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, 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 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, suggest ing that peroxynitrite is produced in contused brain. In protoco 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 CC versus PARP +/+ mice (P < 0.05). However, contusion volume was not different between groups. The results suggest a detri mental effect of PARP on functional outcome after TBI.
Whalen
M J
MJ
Department of Anesthesiology and Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh, Pennsylvania 15260, USA.
Clark
R S
RS
Dixon
C E
CE
Robichaud
P
P
Marion
D W
DW
Vagni
V
V
Graham
S H
SH
Virag
L
L
Hasko
G
G
Stachlewitz
R
R
Szabo
C
C
Kochanek
P M
PM
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D003463:Cues; D007150:Immunohistochemistry; D018782:Maze Learning; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D013028:Space Perception
D011065:Poly(ADP-ribose) Polymerases