| Title |
Inhibition of miR-155 Limits Neuroinflammation and Improves Functional Recovery After Experimental Traumatic Brain Injury in Mice
|
|---|---|
| Published in |
Neurotherapeutics, January 2019
|
| DOI | 10.1007/s13311-018-0665-9 |
| Pubmed ID | |
| Authors |
Rebecca J Henry, Sarah J Doran, James P Barrett, Victoria E Meadows, Boris Sabirzhanov, Bogdan A Stoica, David J Loane, Alan I Faden |
| Abstract |
Micro-RNAs (miRs) are short, noncoding RNAs that negatively regulate gene expression at the post-transcriptional level and have been implicated in the pathophysiology of secondary damage after traumatic brain injury (TBI). Among miRs linked to inflammation, miR-155 has been implicated as a pro-inflammatory factor in a variety of organ systems. We examined the expression profile of miR-155, following experimental TBI (controlled cortical impact) in adult male C57Bl/6 mice, as well as the effects of acute or delayed administration of a miR-155 antagomir on post-traumatic neuroinflammatory responses and neurological recovery. Trauma robustly increased miR-155 expression in the injured cortex over 7 days. Similar TBI-induced miR-155 expression changes were also found in microglia/macrophages isolated from the injured cortex at 7 days post-injury. A miR-155 hairpin inhibitor (antagomir; 0.5 nmol), administered intracerebroventricularly (ICV) immediately after injury, attenuated neuroinflammatory markers at both 1 day and 7 days post-injury and reduced impairments in spatial working memory. Delayed ICV infusion of the miR-155 antagomir (0.5 nmol/day), beginning 24 h post-injury and continuing for 6 days, attenuated neuroinflammatory markers at 7 days post-injury and improved motor, but not cognitive, function through 28 days. The latter treatment limited NADPH oxidase 2 expression changes in microglia/macrophages in the injured cortex and reduced cortical lesion volume. In summary, TBI causes a robust and persistent neuroinflammatory response that is associated with increased miR-155 expression in microglia/macrophages, and miR-155 inhibition reduces post-traumatic neuroinflammatory responses and improves neurological recovery. Thus, miR-155 may be a therapeutic target for TBI-related neuroinflammation. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 83% |
| Ireland | 1 | 17% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 3 | 50% |
| Members of the public | 3 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 66 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 66 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 10 | 15% |
| Student > Ph. D. Student | 9 | 14% |
| Researcher | 9 | 14% |
| Student > Master | 6 | 9% |
| Student > Postgraduate | 4 | 6% |
| Other | 9 | 14% |
| Unknown | 19 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 11 | 17% |
| Biochemistry, Genetics and Molecular Biology | 9 | 14% |
| Medicine and Dentistry | 6 | 9% |
| Agricultural and Biological Sciences | 4 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 5% |
| Other | 9 | 14% |
| Unknown | 24 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 21 September 2018.
All research outputs
#7,717,825
of 25,385,509 outputs
Outputs from Neurotherapeutics
#717
of 1,308 outputs
Outputs of similar age
#148,316
of 446,394 outputs
Outputs of similar age from Neurotherapeutics
#11
of 20 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 1,308 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
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We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.