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Stroke Research and Treatment
Volume 2013 (2013), Article ID 648061, 13 pages
http://dx.doi.org/10.1155/2013/648061
Research Article

Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery

1Stroke Injury and Repair Team, O'Brien Institute, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
2Cytoprotection Pharmacology Program, Centre for Eye Research, The Royal Eye and Ear Hospital Victoria, Melbourne, Victoria, Australia
3Department of Ophthalmology, Faculty of Medicine, The University of Melbourne, Victoria, Australia
4Department of Surgery, Faculty of Medicine, The University of Melbourne, Victoria, Australia

Received 1 November 2012; Accepted 14 December 2012

Academic Editor: Iwa Antonow-Schlorke

Copyright © 2013 Robert M. Weston et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

NADPH oxidase is a major source of superoxide anion following stroke and reperfusion. This study evaluated the effects of apocynin, a known antioxidant and inhibitor of Nox2 NADPH, on neuronal injury and cell-specific responses to stroke induced in the conscious rat. Apocynin treatment (50 mg/kg i.p.) commencing 1 hour prior to stroke and 24 and 48 hours after stroke significantly reduced infarct volume in the cortex by ~ 60%, but had no effect on striatal damage or neurological deficits. In situ detection of reactive oxygen species (ROS) using dihydroethidium fluorescence revealed that increased ROS detected in OX-42 positive cells following ischemia was reduced in apocynin-treated rats by ~ 51%, but surprisingly increased in surrounding NeuN positive cells of the same rats by ~ 27%, in comparison to the contralateral hemisphere. Reduced ROS from activated microglia/macrophages treated with apocynin was associated with reduced Nox2 immunoreactivity without change to the number of cells. These findings confirm the protective effects of apocynin and indicate a novel mechanism via reduced Nox2 expression. We also reveal compensatory changes in neuronal ROS generation as a result of Nox2 inhibition and highlight the need to assess long term individual cell responses to inhibitors of oxidative stress.