| Title |
GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats
|
|---|---|
| Published in |
Molecular Neurobiology, December 2015
|
| DOI | 10.1007/s12035-015-9607-2 |
| Pubmed ID | |
| Authors |
Wei Wang, Mingchang Li, Yuefei Wang, Qian Li, Gang Deng, Jieru Wan, Qingwu Yang, Qianxue Chen, Jian Wang |
| Abstract |
Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke. |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Denmark | 1 | 3% |
| Unknown | 37 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 13% |
| Student > Doctoral Student | 4 | 11% |
| Student > Master | 3 | 8% |
| Student > Ph. D. Student | 3 | 8% |
| Researcher | 3 | 8% |
| Other | 3 | 8% |
| Unknown | 17 | 45% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 4 | 11% |
| Neuroscience | 4 | 11% |
| Medicine and Dentistry | 4 | 11% |
| Agricultural and Biological Sciences | 3 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 8% |
| Other | 1 | 3% |
| Unknown | 19 | 50% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 April 2024.
All research outputs
#7,471,842
of 22,842,950 outputs
Outputs from Molecular Neurobiology
#1,356
of 3,460 outputs
Outputs of similar age
#121,102
of 390,217 outputs
Outputs of similar age from Molecular Neurobiology
#65
of 166 outputs
Altmetric has tracked 22,842,950 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,460 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has gotten more attention than average, scoring higher than 54% of its peers.
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We're also able to compare this research output to 166 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.