Brain ischemic preconditioning does not require PARP-1.

BACKGROUND AND PURPOSE Poly(ADP-ribose) polymerase-1 (PARP-1) is involved in ischemic preconditioning of the heart and cultured neurons, but its role in brain ischemic preconditioning is unknown. Summary of Report- We report that 5-minute bilateral common carotid artery occlusion (BCCAO) in the mouse prompted reduction of infarct volumes triggered 24 hours later by 20-minute middle cerebral artery occlusion (MCAO). Pharmacological PARP-1 inhibition between BCCAO and MCAO did not impair preconditioning. The contents of the PARP-1 substrate NAD, those of its product poly(ADP-ribose), caspase-3 activation, and PARP-1 expression did not change after BCCAO within the preconditioned tissue. PARP-1 KO mice were similarly protected by the 5-minute BCCAO. CONCLUSIONS Data demonstrate that, at variance with the heart, PARP-1 is dispensable for brain ischemic preconditioning.