Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat
We recently showed that inhibition of hypoxia-induced factor-1α (HIF-1α) decreased acute ischemic stroke-induced blood-brain barrier (BBB) damage. However, factors that induce the upregulation of HIF-1α expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a c...
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Wiley
2021-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2021/9928232 |
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| author | Yanping Wang Yufei Shen Xin Yu Jingxia Gu Xiaoling Zhang Beiqun Zhou Yanyun Sun Congying Xu Shuxia Qian |
| author_facet | Yanping Wang Yufei Shen Xin Yu Jingxia Gu Xiaoling Zhang Beiqun Zhou Yanyun Sun Congying Xu Shuxia Qian |
| author_sort | Yanping Wang |
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| description | We recently showed that inhibition of hypoxia-induced factor-1α (HIF-1α) decreased acute ischemic stroke-induced blood-brain barrier (BBB) damage. However, factors that induce the upregulation of HIF-1α expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a critical role in reperfusion-induced BBB damage after stroke. However, the role of NADPH oxidase in BBB injury during the acute ischemia stage remains unclear. This study is aimed at investigating the role of NADPH oxidase in BBB injury and the expression of HIF-1α after acute ischemic stroke. A sutured middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke in rats. Our results show that the inhibition of NADPH oxidase by apocynin can significantly reduce the BBB damage caused by 2 h ischemic stroke accompanied by reducing the degradation of tight junction protein occludin. In addition, treatment with apocynin significantly decreased the upregulation of HIF-1α induced by 2 h MCAO. More importantly, apocynin could also inhibit the MMP-2 upregulation. Of note, HIF-1α was not colocalized with a bigger blood vessel. Taken together, our results showed that inhibition of NADPH oxidase-mediated HIF-1α upregulation reduced BBB damage accompanied by downregulating MMP-2 expression and occludin degradation after 2 h ischemia stroke. These results explored the mechanism of BBB damage after acute ischemic stroke and may help reduce the associated cerebral hemorrhage transformation after thrombolysis and endovascular treatment after ischemic stroke. |
| format | Article |
| id | doaj-art-ec7aecf6a4e24eb29dfb2ec530e9f493 |
| institution | DOAJ |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Neural Plasticity |
| spelling | doaj-art-ec7aecf6a4e24eb29dfb2ec530e9f4932025-08-20T03:21:24ZengWileyNeural Plasticity2090-59041687-54432021-01-01202110.1155/2021/99282329928232Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in RatYanping Wang0Yufei Shen1Xin Yu2Jingxia Gu3Xiaoling Zhang4Beiqun Zhou5Yanyun Sun6Congying Xu7Shuxia Qian8Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, ChinaDepartment of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, ChinaBengbu Medical College (Department of Neurology, The Second Hospital of Jiaxing City), ChinaDepartment of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, ChinaDepartment of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, ChinaDepartment of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, ChinaInstitute of Neuroscience, Soochow University, Suzhou 215123, ChinaDepartment of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, ChinaDepartment of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, ChinaWe recently showed that inhibition of hypoxia-induced factor-1α (HIF-1α) decreased acute ischemic stroke-induced blood-brain barrier (BBB) damage. However, factors that induce the upregulation of HIF-1α expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a critical role in reperfusion-induced BBB damage after stroke. However, the role of NADPH oxidase in BBB injury during the acute ischemia stage remains unclear. This study is aimed at investigating the role of NADPH oxidase in BBB injury and the expression of HIF-1α after acute ischemic stroke. A sutured middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke in rats. Our results show that the inhibition of NADPH oxidase by apocynin can significantly reduce the BBB damage caused by 2 h ischemic stroke accompanied by reducing the degradation of tight junction protein occludin. In addition, treatment with apocynin significantly decreased the upregulation of HIF-1α induced by 2 h MCAO. More importantly, apocynin could also inhibit the MMP-2 upregulation. Of note, HIF-1α was not colocalized with a bigger blood vessel. Taken together, our results showed that inhibition of NADPH oxidase-mediated HIF-1α upregulation reduced BBB damage accompanied by downregulating MMP-2 expression and occludin degradation after 2 h ischemia stroke. These results explored the mechanism of BBB damage after acute ischemic stroke and may help reduce the associated cerebral hemorrhage transformation after thrombolysis and endovascular treatment after ischemic stroke.http://dx.doi.org/10.1155/2021/9928232 |
| spellingShingle | Yanping Wang Yufei Shen Xin Yu Jingxia Gu Xiaoling Zhang Beiqun Zhou Yanyun Sun Congying Xu Shuxia Qian Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat Neural Plasticity |
| title | Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat |
| title_full | Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat |
| title_fullStr | Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat |
| title_full_unstemmed | Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat |
| title_short | Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat |
| title_sort | role of nadph oxidase induced hypoxia induced factor 1α increase in blood brain barrier disruption after 2 hour focal ischemic stroke in rat |
| url | http://dx.doi.org/10.1155/2021/9928232 |
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