TY - JOUR
T1 - Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase
AU - Whalen, Michael J.
AU - Clark, Robert S.B.
AU - Dixon, C. Edward
AU - Robichaud, Paul
AU - Marion, Donald W.
AU - Vagni, Vincent
AU - Graham, Steven H.
AU - Virag, Laszlo
AU - Hasko, Gyorgy
AU - Stachlewitz, Robert
AU - Szabo, Csaba
AU - Kochanek, Patrick M.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Brain injury
KW - Controlled cortical impact
KW - Mice
KW - Poly(ADP-ribose) polymerase
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U2 - 10.1097/00004647-199908000-00002
DO - 10.1097/00004647-199908000-00002
M3 - Article
C2 - 10458590
AN - SCOPUS:17544364526
SN - 0271-678X
VL - 19
SP - 835
EP - 842
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 8
ER -