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| Content Provider | Springer Nature Link |
|---|---|
| Author | Sang, Hongfei Qiu, Zhongming Cai, Jin Lan, Wenya Yu, Linjie Zhang, Hao Li, Min Xie, Yi Guo, Ruibing Ye, Ruidong Liu, Xinfeng Liu, Ling Zhang, Renliang |
| Copyright Year | 2017 |
| Abstract | Hemorrhagic transformation (HT) is a major complication of ischemic stroke and further deteriorates neurological outcomes. Bradykinin 1 receptor (B1R) has been proven to mediate vasculo-toxicity in various experimental models. However, its role in the development of HT after stroke remains unclear. We detected the B1R expression in brain tissues with or without HT in a rat model of cerebral ischemia/reperfusion (I/R) with type 1 diabetes, showing higher B1R expression in the hemorrhagic areas than the ischemic tissues. Then, B1R agonist or antagonist was administrated intravenously just before reperfusion to investigate its effect on HT and the underlying molecular mechanism. Administration of low (300 nmol/kg) or high (1 μmol/kg) dose of B1R antagonist mitigated hemorrhage, improved neurobehavioral deficits, and preserved blood-brain-barrier (BBB) integrity after reperfusion for 8 h whereas the 300 nmol/kg of B1R agonist aggravated these outcomes, though only the high does of B1R antagonist affected the infarction volume. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was increased by B1R activation but decreased by B1R inhibition, which mediated B1R toxicity on BBB disruption and ischemia-related HT. Furthermore, B1R activation facilitated the mRNA and protein expressions of MMP-9 in the hemorrhagic tissues, and these increases were blocked by both ERK inhibitor U0126 and NF-κB inhibitor PDTC. U0126 also remarkably decreased the B1R-induced NF-κB/p65 activation. We concluded that upregulated B1R may contribute to early HT after I/R in type 1 diabetic rats via ERK1/2/NF-κB/MMP-9 pathway. B1R inhibition could be an encouraging therapeutic strategy to withstand HT after ischemic stroke in diabetic patients. |
| Starting Page | 597 |
| Ending Page | 611 |
| Page Count | 15 |
| File Format | |
| ISSN | 18684483 |
| Journal | Translational Stroke Research |
| Volume Number | 8 |
| Issue Number | 6 |
| e-ISSN | 1868601X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2017-07-19 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Type 1 diabetes mellitus Intracerebral hemorrhage Bradykinin 1 receptor Extracellular signal-regulated kinase Matrix metalloproteinase-9 Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical) |
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