Differential Effect of PARP-2 Deletion on Brain Injury after Focal and Global Cerebral Ischemia

DOI Web Site Web Site 被引用文献2件
  • Julia Kofler
    Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA
  • Takashi Otsuka
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
  • Zhizheng Zhang
    Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA
  • Ruediger Noppens
    Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA
  • Marjorie R Grafe
    Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA
  • David W Koh
    Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
  • Valina L Dawson
    Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
  • Josiane Ménissier de Murcia
    Unité 9003 du CNRS, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch Cedex, France
  • Patricia D Hurn
    Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA
  • Richard J Traystman
    Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA

説明

<jats:p> 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<jats:sup>−/-</jats:sup> 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 KCl-induced cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) and 3-day survival. After MCAO, infarct volume was reduced in PARP-2<jats:sup>−/-</jats:sup>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. </jats:p>

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