Differential effect of PARP-2 deletion on brain injury after focal and global cerebral ischemia

Julia Kofler, Takashi Otsuka, Zhizheng Zhang, Ruediger Noppens, Marjorie R. Grafe, David W. Koh, Valina L. Dawson, Josiane Ménissier De Murcia, Patricia D. Hurn, Richard J. Traystman

Research output: Contribution to journalArticle

Abstract

Poly(ADP-ribose) polymerase-2 (PARP-2) is a member of the PARP enzyme family, and, similarly to PARP-1, catalyzes the formation of ADP-ribose polymers in response to DNA damage. While PARP-1 overactivation contributes to ischemic cell death, no information is available regarding the role of PARP-2. In this study, we evaluated the impact of PARP-2 deletion on histopathological outcome from two different experimental models of cerebral ischemia. Male PARP-2 -/- mice and wild-type (WT) littermates were subjected to either 2 h of middle cerebral artery occlusion (MCAO) followed by 22 h reperfusion, or underwent 10 mins of KCI-induced cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) and 3-day survival. After MCAO, infarct volume was reduced in PARP-2-/- mice (38%±12% of contralateral hemisphere) compared with WT (64%±16%). After CA/CPR, PARP-2 deletion significantly increased neuronal cell loss in the hippocampal CA1 field (65%±36% ischemic neurons) when compared with WT mice (31%±33%), with no effect in either striatum or cortex. We conclude that PARP-2 is a novel executioner of cell death pathways in focal cerebral ischemia, but might be a necessary survival factor after global ischemia to mitigate hippocampal delayed cell death.

Original languageEnglish (US)
Pages (from-to)135-141
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2006

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Keywords

  • Cardiac arrest
  • Middle cerebral artery occlusion
  • Neuroprotection
  • Poly(ADP-ribose) polymerase-2

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Kofler, J., Otsuka, T., Zhang, Z., Noppens, R., Grafe, M. R., Koh, D. W., Dawson, V. L., De Murcia, J. M., Hurn, P. D., & Traystman, R. J. (2006). Differential effect of PARP-2 deletion on brain injury after focal and global cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism, 26(1), 135-141. https://doi.org/10.1038/sj.jcbfm.9600173