Differential effect of PARP-2 deletion on brain injury after focal and global cerebral ischemia.
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.
Kofler
Julia
J
Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
Otsuka
Takashi
T
Zhang
Zhizheng
Z
Noppens
Ruediger
R
Grafe
Marjorie R
MR
Koh
David W
DW
Dawson
Valina L
VL
de Murcia
Josiane Ménissier
JM
Hurn
Patricia D
PD
Traystman
Richard J
RJ
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016887:Cardiopulmonary Resuscitation; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000139:chemically induced / Q000150:complications; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000378:metabolism*; D011189:Potassium Chloride / Q000737:chemistry; D015424:Reperfusion
D011189:Potassium Chloride; D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse