Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery
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...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Stroke Research and Treatment |
| Online Access: | http://dx.doi.org/10.1155/2013/648061 |
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| author | Robert M. Weston Bin Lin Gregory J. Dusting Carli L. Roulston |
| author_facet | Robert M. Weston Bin Lin Gregory J. Dusting Carli L. Roulston |
| author_sort | Robert M. Weston |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5cfe927aaad1496d985858ecd1171cea |
| institution | Kabale University |
| issn | 2090-8105 2042-0056 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stroke Research and Treatment |
| spelling | doaj-art-5cfe927aaad1496d985858ecd1171cea2025-02-03T01:26:43ZengWileyStroke Research and Treatment2090-81052042-00562013-01-01201310.1155/2013/648061648061Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term RecoveryRobert M. Weston0Bin Lin1Gregory J. Dusting2Carli L. Roulston3Stroke Injury and Repair Team, O’Brien Institute, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, AustraliaStroke Injury and Repair Team, O’Brien Institute, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, AustraliaCytoprotection Pharmacology Program, Centre for Eye Research, The Royal Eye and Ear Hospital Victoria, Melbourne, Victoria, AustraliaStroke Injury and Repair Team, O’Brien Institute, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, AustraliaNADPH 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.http://dx.doi.org/10.1155/2013/648061 |
| spellingShingle | Robert M. Weston Bin Lin Gregory J. Dusting Carli L. Roulston Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery Stroke Research and Treatment |
| title | Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery |
| title_full | Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery |
| title_fullStr | Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery |
| title_full_unstemmed | Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery |
| title_short | Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats: Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery |
| title_sort | targeting oxidative stress injury after ischemic stroke in conscious rats limited benefits with apocynin highlight the need to incorporate long term recovery |
| url | http://dx.doi.org/10.1155/2013/648061 |
| work_keys_str_mv | AT robertmweston targetingoxidativestressinjuryafterischemicstrokeinconsciousratslimitedbenefitswithapocyninhighlighttheneedtoincorporatelongtermrecovery AT binlin targetingoxidativestressinjuryafterischemicstrokeinconsciousratslimitedbenefitswithapocyninhighlighttheneedtoincorporatelongtermrecovery AT gregoryjdusting targetingoxidativestressinjuryafterischemicstrokeinconsciousratslimitedbenefitswithapocyninhighlighttheneedtoincorporatelongtermrecovery AT carlilroulston targetingoxidativestressinjuryafterischemicstrokeinconsciousratslimitedbenefitswithapocyninhighlighttheneedtoincorporatelongtermrecovery |