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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Thrombin, a mediator of cerebrovascular inflammation in AD and hypoxia
|
|---|---|
| Published in |
Frontiers in Aging Neuroscience, January 2013
|
| DOI | 10.3389/fnagi.2013.00019 |
| Pubmed ID | |
| Authors |
Debjani Tripathy, Alma Sanchez, Xiangling Yin, Jinhua Luo, Joseph Martinez, Paula Grammas |
| Abstract |
Considerable evidence implicates hypoxia and vascular inflammation in Alzheimer's disease (AD). Thrombin, a multifunctional inflammatory mediator, is demonstrable in the brains of AD patients both in the vessel walls and senile plaques. Hypoxia-inducible factor 1α (HIF-1α), a key regulator of the cellular response to hypoxia, is also upregulated in the vasculature of human AD brains. The objective of this study is to investigate inflammatory protein expression in the cerebrovasculature of transgenic AD mice and to explore the role of thrombin as a mediator of cerebrovascular inflammation and oxidative stress in AD and in hypoxia-induced changes in brain endothelial cells. Immunofluorescent analysis of the cerebrovasculature in AD mice demonstrates significant (p < 0.01-0.001) increases in thrombin, HIF-1α, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) compared to controls. Administration of the thrombin inhibitor dabigatran (100 mg/kg) to AD mice for 34 weeks significantly decreases expression of inflammatory proteins and ROS. Exposure of cultured brain endothelial cells to hypoxia for 6 h causes an upregulation of thrombin, HIF-1α, MCP-1, IL-6, and MMP2 and ROS. Treatment of endothelial cells with the dabigatran (1 nM) reduces ROS generation and inflammatory protein expression (p < 0.01-0.001). The data demonstrate that inhibition of thrombin in culture blocks the increase in inflammatory protein expression and ROS generation evoked by hypoxia. Also, administration of dabigatran to transgenic AD mice diminishes ROS levels in brain and reduces cerebrovascular expression of inflammatory proteins. Taken together, these results suggest that inhibiting thrombin generation could have therapeutic value in AD and other disorders where hypoxia, inflammation, and oxidative stress are involved. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 1 | 25% |
| United States | 1 | 25% |
| Unknown | 2 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 78 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Colombia | 1 | 1% |
| United States | 1 | 1% |
| Switzerland | 1 | 1% |
| Unknown | 75 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 14 | 18% |
| Researcher | 13 | 17% |
| Student > Ph. D. Student | 13 | 17% |
| Student > Bachelor | 8 | 10% |
| Student > Doctoral Student | 5 | 6% |
| Other | 14 | 18% |
| Unknown | 11 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 17 | 22% |
| Neuroscience | 12 | 15% |
| Biochemistry, Genetics and Molecular Biology | 9 | 12% |
| Medicine and Dentistry | 9 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 9% |
| Other | 8 | 10% |
| Unknown | 16 | 21% |
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 25 November 2021.
All research outputs
#5,859,981
of 22,710,079 outputs
Outputs from Frontiers in Aging Neuroscience
#2,301
of 4,730 outputs
Outputs of similar age
#61,977
of 280,729 outputs
Outputs of similar age from Frontiers in Aging Neuroscience
#27
of 77 outputs
Altmetric has tracked 22,710,079 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 4,730 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.1. This one has gotten more attention than average, scoring higher than 51% 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 280,729 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 77% of its contemporaries.
We're also able to compare this research output to 77 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 64% of its contemporaries.