TY - JOUR
T1 - Differential effect of PARP-2 deletion on brain injury after focal and global cerebral ischemia
AU - Kofler, Julia
AU - Otsuka, Takashi
AU - Zhang, Zhizheng
AU - Noppens, Ruediger
AU - Grafe, Marjorie R.
AU - Koh, David W.
AU - Dawson, Valina L.
AU - De Murcia, Josiane Ménissier
AU - Hurn, Patricia D.
AU - Traystman, Richard J.
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
KW - Cardiac arrest
KW - Middle cerebral artery occlusion
KW - Neuroprotection
KW - Poly(ADP-ribose) polymerase-2
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U2 - 10.1038/sj.jcbfm.9600173
DO - 10.1038/sj.jcbfm.9600173
M3 - Article
C2 - 15959455
AN - SCOPUS:29144446064
SN - 0271-678X
VL - 26
SP - 135
EP - 141
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 1
ER -