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Novel TNF receptor-1 inhibitors identified as potential therapeutic candidates for traumatic brain injury

Overview of attention for article published in Journal of Neuroinflammation, May 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (68th percentile)

Mentioned by

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11 tweeters

Citations

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3 Dimensions

Readers on

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21 Mendeley
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Title
Novel TNF receptor-1 inhibitors identified as potential therapeutic candidates for traumatic brain injury
Published in
Journal of Neuroinflammation, May 2018
DOI 10.1186/s12974-018-1200-y
Pubmed ID
Authors

Rachel K. Rowe, Jordan L. Harrison, Hongtao Zhang, Adam D. Bachstetter, David P. Hesson, Bruce F. O’Hara, Mark I. Greene, Jonathan Lifshitz

Abstract

Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio-indicator of inflammation. We hypothesized the efficacy of novel TNF receptor (TNF-R) inhibitors could be screened using post-traumatic sleep and that these novel compounds would improve functional recovery following diffuse TBI in the mouse. Three inhibitors of TNF-R activation were synthesized based on the structure of previously reported TNF CIAM inhibitor F002, which lodges into a defined TNFR1 cavity at the TNF-binding interface, and screened for in vitro efficacy of TNF pathway inhibition (IκB phosphorylation). Compounds were screened for in vivo efficacy in modulating post-traumatic sleep. Compounds were then tested for efficacy in improving functional recovery and verification of cellular mechanism. Brain-injured mice treated with Compound 7 (C7) or SGT11 slept significantly less than those treated with vehicle, suggesting a therapeutic potential to target neuroinflammation. SGT11 restored cognitive, sensorimotor, and neurological function. C7 and SGT11 significantly decreased cortical inflammatory cytokines 3 h post-TBI. Using sleep as a bio-indicator of TNF-R-dependent neuroinflammation, we identified C7 and SGT11 as potential therapeutic candidates for TBI.

Twitter Demographics

The data shown below were collected from the profiles of 11 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 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 43%
Unspecified 4 19%
Student > Master 3 14%
Student > Doctoral Student 2 10%
Other 1 5%
Other 2 10%
Readers by discipline Count As %
Unspecified 7 33%
Neuroscience 4 19%
Nursing and Health Professions 2 10%
Medicine and Dentistry 2 10%
Agricultural and Biological Sciences 2 10%
Other 4 19%

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 09 April 2019.
All research outputs
#3,334,640
of 13,605,490 outputs
Outputs from Journal of Neuroinflammation
#408
of 1,582 outputs
Outputs of similar age
#83,575
of 271,085 outputs
Outputs of similar age from Journal of Neuroinflammation
#1
of 1 outputs
Altmetric has tracked 13,605,490 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,582 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 74% 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 271,085 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 68% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them