1. ¹Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA
2. ²Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
3. ³Department of Pathology, Oregon Health and Science University, Portland, Oregon, USA
4. ⁴Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
5. ⁵Unité 9003 du CNRS, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch Cedex, France

Correspondence: Professor RJ Traystman, Department of Anesthesiology and Perioperative Medicine, Research Planning and Development, Basic Research, School of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail Code UHS-2, Multnomah Pavillion Room 3413, Portland, OR 97239, USA. E-mail: traystma@ohsu.edu

Received 4 January 2005; Revised 7 April 2005; Accepted 22 April 2005; Published online 15 June 2005.

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 KCl-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.