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,...
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Published in | Journal of cerebral blood flow and metabolism Vol. 19; no. 8; pp. 835 - 842 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article Conference Proceeding |
Language | English |
Published |
London, England
SAGE Publications
01.08.1999
Lippincott Williams & Wilkins |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0271-678X 1559-7016 |
DOI: | 10.1097/00004647-199908000-00002 |