Title |
Inhibition of HIF-1α Reduced Blood Brain Barrier Damage by Regulating MMP-2 and VEGF During Acute Cerebral Ischemia
|
---|---|
Published in |
Frontiers in Cellular Neuroscience, September 2018
|
DOI | 10.3389/fncel.2018.00288 |
Pubmed ID | |
Authors |
Yufei Shen, Jingxia Gu, Ziyun Liu, Congying Xu, Shuxia Qian, Xiaoling Zhang, Beiqun Zhou, Qiaobing Guan, Yanyun Sun, Yanping Wang, Xinchun Jin |
Abstract |
Increase of blood brain barrier (BBB) permeability after acute ischemia stroke is a predictor to intracerebral hemorrhage transformation (HT) for tissue plasminogen activator (tPA) thrombolysis and post-endovascular treatment. Previous studies showed that 2-h ischemia induced damage of BBB integrity and matrix metalloproteinase-2 (MMP-2) made major contribution to this disruption. A recent study showed that blocking β2-adrenergic receptor (β2-AR) alleviated ischemia-induced BBB injury by reducing hypoxia-inducible factor-1 alpha (HIF-1α) level. In this study, we sought to investigate the interaction of HIF-1α with MMP-2 and vascular endothelial growth factor (VEGF) in BBB injury after acute ischemia stroke. Rat suture middle cerebral artery occlusion (MCAO) model was used to mimic ischemia condition. Our results showed that ischemia produced BBB damage and MMP-2/9 upregulation was colocalized with Rhodamine-dextran leakage. Pretreatment with YC-1, a HIF-1α inhibitor, alleviated 2-h ischemia-induced BBB injury significantly accompanied by decrease of MMP-2 upregulation. In addition, YC-1 also prevented VEGF-induced BBB damage. Of note, VEGF was shown to be colocalized with neurons but not astrocytes. Taken together, BBB damage was reduced by inhibition of interaction of HIF-1α with MMP-2 and VEGF during acute cerebral ischemia. These findings provide mechanisms underlying BBB damage after acute ischemia stroke and may help reduce thrombolysis- and post-endovascular treatment-related cerebral hemorrhage. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 4 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 46 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 8 | 17% |
Student > Ph. D. Student | 7 | 15% |
Student > Bachelor | 5 | 11% |
Professor | 4 | 9% |
Professor > Associate Professor | 4 | 9% |
Other | 7 | 15% |
Unknown | 11 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 10 | 22% |
Pharmacology, Toxicology and Pharmaceutical Science | 9 | 20% |
Medicine and Dentistry | 5 | 11% |
Biochemistry, Genetics and Molecular Biology | 4 | 9% |
Agricultural and Biological Sciences | 2 | 4% |
Other | 6 | 13% |
Unknown | 10 | 22% |