| Title |
The Synergistic Combination of Everolimus and Paroxetine Exerts Post-ischemic Neuroprotection In Vitro
|
|---|---|
| Published in |
Cellular and Molecular Neurobiology, July 2018
|
| DOI | 10.1007/s10571-018-0605-6 |
| Pubmed ID | |
| Authors |
V. S. Suvanish Kumar, Etheresia Pretorius, G. K. Rajanikant |
| Abstract |
Ischemic stroke is a debilitating multi-factorial cerebrovascular disorder, representing an area of tremendous unmet medical need. Combination treatment has been proposed as a promising therapeutic approach towards combating ischemic stroke. The present study employs in vitro oxygen glucose deprivation (OGD) model to evaluate the post-ischemic neuroprotective efficacy of Everolimus and Paroxetine, alone and in combination. Post-OGD treatment with Everolimus and Paroxetine, alone or in combination, significantly improved the cell survival (~ 80%) when compared to the cells subjected to ischemic injury alone. The individual neuroprotective doses of Everolimus and Paroxetine were found to be at 6.25 and 25 nM, respectively. Whereas, the synergistic neuroprotective dose for Everolimus:Paroxetine was 2:10 nM, calculated using the Chou-Talalay combination index and other four mathematical models. The synergistic combination dose downregulated neuroinflammatory genes (Tnf-α, Il1b, Nf-κB, and iNos) and upregulated the neuroprotective genes (Bcl-2, Bcl-xl, Hif-1, and Epo). The mitochondrial functioning and ROS neutralizing ability increased with combination treatment. Further, the active role of nitric oxide synthase and calmodulin were revealed while exploring the bio-activity of Everolimus and Paroxetine through network pharmacology. The present study for the first time demonstrates the synergistic post-ischemic neuroprotective efficacy of combination treatment with Everolimus and Paroxetine in vitro. Taken together, these findings clearly suggest that Everolimus in combination with Paroxetine may represent a promising therapeutic strategy for the treatment of ischemic stroke, further supporting the combination treatment strategy for this debilitating disorder. |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 3 | 19% |
| Student > Doctoral Student | 2 | 13% |
| Student > Master | 2 | 13% |
| Student > Bachelor | 1 | 6% |
| Librarian | 1 | 6% |
| Other | 2 | 13% |
| Unknown | 5 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 38% |
| Neuroscience | 2 | 13% |
| Biochemistry, Genetics and Molecular Biology | 1 | 6% |
| Veterinary Science and Veterinary Medicine | 1 | 6% |
| Social Sciences | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 4 | 25% |
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 30 July 2020.
All research outputs
#8,383,842
of 25,047,899 outputs
Outputs from Cellular and Molecular Neurobiology
#373
of 1,086 outputs
Outputs of similar age
#132,843
of 335,682 outputs
Outputs of similar age from Cellular and Molecular Neurobiology
#6
of 10 outputs
Altmetric has tracked 25,047,899 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,086 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
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We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.