on November 5, 2009
Published online before print November 5, 2009, doi: 10.1161/STROKEAHA.109.567826
Submitted on September 11, 2009
From the Department of Pharmacology (G.F., F.B., F.M., A.C.), University of Florence, Italy; and the Leibniz Institute of Age Research (W.M., Z.-Q.W.), Fritz Lipmann Institute, Jena, Germany; and Faculty of Biology and Pharmacy (Z.-Q.W.), Friedrich-Schiller-University Jena, Jena, Germany. * To whom correspondence should be addressed. E-mail: alberto.chiarugi{at}unifi.it.
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. Conclusion—Data demonstrate that, at variance with the heart, PARP-1 is dispensable for brain ischemic preconditioning.
Revised on October 2, 2009
Accepted on October 13, 2009
Brain Ischemic Preconditioning Does Not Require PARP-1
Giuseppe Faraco MD;
Key words: neuroprotectants • poly(ADP-ribose) • PARP • NAD • ATP