Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase

Michael J. Whalen, Robert S B Clark, C. Edward Dixon, Paul Robichaud, Donald W. Marion, Vincent Vagni, Steven H. Graham, Laszlo Virag, Gyorgy Hasko, Robert Stachlewitz, Csaba Szabo, Patrick M. Kochanek

Research output: Contribution to journalArticle

129 Citations (Scopus)

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 (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.

Original languageEnglish (US)
Pages (from-to)835-842
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume19
Issue number8
StatePublished - 1999
Externally publishedYes

Fingerprint

Poly(ADP-ribose) Polymerases
Contusions
Peroxynitrous Acid
Poly Adenosine Diphosphate Ribose
Traumatic Brain Injury
Ligases
NAD
DNA Damage
Tyrosine
Staining and Labeling
Brain
Enzymes

Keywords

  • Brain injury
  • Controlled cortical impact
  • Mice
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Whalen, M. J., Clark, R. S. B., Dixon, C. E., Robichaud, P., Marion, D. W., Vagni, V., ... Kochanek, P. M. (1999). Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase. Journal of Cerebral Blood Flow and Metabolism, 19(8), 835-842.

Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase. / 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.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 19, No. 8, 1999, p. 835-842.

Research output: Contribution to journalArticle

Whalen, MJ, Clark, RSB, Dixon, CE, Robichaud, P, Marion, DW, Vagni, V, Graham, SH, Virag, L, Hasko, G, Stachlewitz, R, Szabo, C & Kochanek, PM 1999, 'Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase', Journal of Cerebral Blood Flow and Metabolism, vol. 19, no. 8, pp. 835-842.
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. / Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase. In: Journal of Cerebral Blood Flow and Metabolism. 1999 ; Vol. 19, No. 8. pp. 835-842.
@article{abbb376ccdd74a8496f22d36fd827151,
title = "Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase",
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 (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.",
keywords = "Brain injury, Controlled cortical impact, Mice, Poly(ADP-ribose) polymerase",
author = "Whalen, {Michael J.} and Clark, {Robert S B} and Dixon, {C. Edward} and Paul Robichaud and Marion, {Donald W.} and Vincent Vagni and Graham, {Steven H.} and Laszlo Virag and Gyorgy Hasko and Robert Stachlewitz and Csaba Szabo and Kochanek, {Patrick M.}",
year = "1999",
language = "English (US)",
volume = "19",
pages = "835--842",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "8",

}

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

UR - http://www.scopus.com/inward/record.url?scp=17544364526&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17544364526&partnerID=8YFLogxK

M3 - Article

C2 - 10458590

AN - SCOPUS:17544364526

VL - 19

SP - 835

EP - 842

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 8

ER -