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Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit

Overview of attention for article published in Journal of Neuroinflammation, December 2016
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#26 of 2,139)
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
8 news outlets
twitter
7 tweeters

Citations

dimensions_citation
100 Dimensions

Readers on

mendeley
183 Mendeley
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Title
Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit
Published in
Journal of Neuroinflammation, December 2016
DOI 10.1186/s12974-016-0760-y
Pubmed ID
Authors

Jacquelyn A. Brown, Simona G. Codreanu, Mingjian Shi, Stacy D. Sherrod, Dmitry A. Markov, M. Diana Neely, Clayton M. Britt, Orlando S. Hoilett, Ronald S. Reiserer, Philip C. Samson, Lisa J. McCawley, Donna J. Webb, Aaron B. Bowman, John A. McLean, John P. Wikswo

Abstract

Understanding blood-brain barrier responses to inflammatory stimulation (such as lipopolysaccharide mimicking a systemic infection or a cytokine cocktail that could be the result of local or systemic inflammation) is essential to understanding the effect of inflammatory stimulation on the brain. It is through the filter of the blood-brain barrier that the brain responds to outside influences, and the blood-brain barrier is a critical point of failure in neuroinflammation. It is important to note that this interaction is not a static response, but one that evolves over time. While current models have provided invaluable information regarding the interaction between cytokine stimulation, the blood-brain barrier, and the brain, these approaches-whether in vivo or in vitro-have often been only snapshots of this complex web of interactions. We utilize new advances in microfluidics, organs-on-chips, and metabolomics to examine the complex relationship of inflammation and its effects on blood-brain barrier function ex vivo and the metabolic consequences of these responses and repair mechanisms. In this study, we pair a novel dual-chamber, organ-on-chip microfluidic device, the NeuroVascular Unit, with small-volume cytokine detection and mass spectrometry analysis to investigate how the blood-brain barrier responds to two different but overlapping drivers of neuroinflammation, lipopolysaccharide and a cytokine cocktail of IL-1β, TNF-α, and MCP1,2. In this study, we show that (1) during initial exposure to lipopolysaccharide, the blood-brain barrier is compromised as expected, with increased diffusion and reduced presence of tight junctions, but that over time, the barrier is capable of at least partial recovery; (2) a cytokine cocktail also contributes to a loss of barrier function; (3) from this time-dependent cytokine activation, metabolic signature profiles can be obtained for both the brain and vascular sides of the blood-brain barrier model; and (4) collectively, we can use metabolite analysis to identify critical pathways in inflammatory response. Taken together, these findings present new data that allow us to study the initial effects of inflammatory stimulation on blood-brain barrier disruption, cytokine activation, and metabolic pathway changes that drive the response and recovery of the barrier during continued inflammatory exposure.

Twitter Demographics

The data shown below were collected from the profiles of 7 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 183 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Portugal 1 <1%
Unknown 181 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 41 22%
Student > Master 32 17%
Researcher 27 15%
Student > Bachelor 25 14%
Student > Doctoral Student 13 7%
Other 19 10%
Unknown 26 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 31 17%
Engineering 30 16%
Neuroscience 22 12%
Agricultural and Biological Sciences 20 11%
Chemistry 8 4%
Other 29 16%
Unknown 43 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 59. 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 28 August 2017.
All research outputs
#434,107
of 17,363,630 outputs
Outputs from Journal of Neuroinflammation
#26
of 2,139 outputs
Outputs of similar age
#14,587
of 397,624 outputs
Outputs of similar age from Journal of Neuroinflammation
#4
of 179 outputs
Altmetric has tracked 17,363,630 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,139 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one has done particularly well, scoring higher than 98% 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 397,624 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 179 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.