| Title |
TRPV4 Activation Contributes Functional Recovery from Ischemic Stroke via Angiogenesis and Neurogenesis
|
|---|---|
| Published in |
Molecular Neurobiology, June 2017
|
| DOI | 10.1007/s12035-017-0625-0 |
| Pubmed ID | |
| Authors |
Chun-Kai Chen, Po-Yuan Hsu, Tzu-Ming Wang, Zhi-Feng Miao, Ruey-Tay Lin, Suh-Hang H. Juo |
| Abstract |
The endothelial transient receptor potential cation channel subfamily V member 4 (TRPV4) plays a crucial role in vascular remodeling; however, TRPV4-mediated angiogenesis after ischemic neuronal death as a neurorestorative strategy has not yet been thoroughly examined. In this study, we first tested whether TRPV4 activation can improve functional recovery in rats subjected to transient brain ischemia. The possible mechanisms for TRPV4 activation-promoted functional recovery were explored. A TRPV4 agonist, 4α-phorbol 12,13-didecanoate (4α-PDD), was intravenously injected via the tail vein at 6 h and 1, 2, 3, 4 days after ischemic stroke. The treatment reduced infarct volume by almost 50% (14.7 ± 3.7 vs. 29.2 ± 6.2%; p < 0.0001) and improved functional outcomes (p = 0.03) on day 5. To explore the therapeutic mechanism, we measured endothelial nitric oxide synthase (eNOS) expression and phosphorylation, vascular endothelial growth factor A (VEGFA) signaling, and neural stem/progenitor cells (NPCs). TRPV4 activation significantly increased eNOS expression and phosphorylation (serine 1177) by more than 2-fold in the ischemic region. The expressions of VEGFA and VEGF receptor-2 were significantly higher in the treated animals, especially an increase of the proangiogenic VEGFA164a isoform while a decrease of the antiangiogenic VEGFA165b isoform. We evaluated angiogenesis by detecting microvessel density in ischemic region. Using the immunohistochemistry staining, we found that 4α-PDD treatment caused a 3.4-fold increase of microvessel density (p < 0.0001). In addition, NPC proliferation and migration in the ischemic hemisphere were increased by 3-fold and 5-fold, respectively. In conclusion, our data suggest that TRPV4 activation by 4α-PDD may improve poststroke functional improvement through angiogenesis and neurogenesis. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Sweden | 1 | 2% |
| Unknown | 41 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 17% |
| Student > Bachelor | 6 | 14% |
| Student > Ph. D. Student | 6 | 14% |
| Student > Doctoral Student | 3 | 7% |
| Student > Master | 3 | 7% |
| Other | 7 | 17% |
| Unknown | 10 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 21% |
| Neuroscience | 7 | 17% |
| Medicine and Dentistry | 5 | 12% |
| Unspecified | 2 | 5% |
| Immunology and Microbiology | 2 | 5% |
| Other | 4 | 10% |
| Unknown | 13 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 August 2020.
All research outputs
#6,344,052
of 22,979,862 outputs
Outputs from Molecular Neurobiology
#1,222
of 3,481 outputs
Outputs of similar age
#101,892
of 317,132 outputs
Outputs of similar age from Molecular Neurobiology
#42
of 128 outputs
Altmetric has tracked 22,979,862 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 3,481 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 64% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 317,132 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 128 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 67% of its contemporaries.