The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals

The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals Poly(ADP‐ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3‐aminobenzamide (3‐AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3‐AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague–Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague–Dawley rats were used for sham operation. 3‐AB was administered to 85 rats 10 min before the occlusion (3‐AB group (n = 85) vs. control group without 3‐AB (n = 85)). Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)‐mediated dUTP‐biotin nick end‐labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP‐ribose) polymer (PAR), cleaved caspase‐3, CD11b, intercellular adhesion molecule‐1 (ICAM‐1), cyclooxygenase‐2 (COX‐2), phospho‐Akt (pAkt) and phospho‐glycogen synthase kinase‐3 (pGSK‐3) were compared in the peri‐infarcted region of the 3‐AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3‐AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL‐positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase‐3, CD11b, ICAM‐1 and COX‐2 were significantly reduced, while the IRs of pAkt and pGSK‐3 were increased. These results suggest that 3‐AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

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Publisher
Wiley
Copyright
Copyright © 2004 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1111/j.1460-9568.2004.03632.x
Publisher site
See Article on Publisher Site

Abstract

Poly(ADP‐ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3‐aminobenzamide (3‐AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3‐AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague–Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague–Dawley rats were used for sham operation. 3‐AB was administered to 85 rats 10 min before the occlusion (3‐AB group (n = 85) vs. control group without 3‐AB (n = 85)). Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)‐mediated dUTP‐biotin nick end‐labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP‐ribose) polymer (PAR), cleaved caspase‐3, CD11b, intercellular adhesion molecule‐1 (ICAM‐1), cyclooxygenase‐2 (COX‐2), phospho‐Akt (pAkt) and phospho‐glycogen synthase kinase‐3 (pGSK‐3) were compared in the peri‐infarcted region of the 3‐AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3‐AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL‐positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase‐3, CD11b, ICAM‐1 and COX‐2 were significantly reduced, while the IRs of pAkt and pGSK‐3 were increased. These results suggest that 3‐AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke.

Journal

European Journal of NeuroscienceWiley

Published: Sep 1, 2004

References

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    Besson, Besson; Croci, Croci; Boulu, Boulu; Plotkine, Plotkine; Marchand‐Verrecchia, Marchand‐Verrecchia
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    Cosi, Cosi; Suzuki, Suzuki; Milani, Milani; Facci, Facci; Menegazzi, Menegazzi; Vantini, Vantini; Kanai, Kanai; Skaper, Skaper
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    Couturier, Couturier; Ding‐Zhou, Ding‐Zhou; Croci, Croci; Plotkine, Plotkine; Margaill, Margaill
  • Effect of poly (ADP‐ribose) polymerase inhibitors on oxidative stress evoked hydroxyl radical level and macromolecules oxidation in cell free system of rat brain cortex
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