| Title |
Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury
|
|---|---|
| Published in |
Pharmaceutical Research, March 2017
|
| DOI | 10.1007/s11095-017-2130-6 |
| Pubmed ID | |
| Authors |
Gerald A. Higgins, Patrick Georgoff, Vahagn Nikolian, Ari Allyn-Feuer, Brian Pauls, Richard Higgins, Brian D. Athey, Hasan E. Alam |
| Abstract |
To determine the mechanism of action of valproic acid (VPA) in the adult central nervous system (CNS) following traumatic brain injury (TBI) and hemorrhagic shock (HS). Data were analyzed from different sources, including experiments in a porcine model, data from postmortem human brain, published studies, public and commercial databases. The transcriptional program in the CNS following TBI, HS, and VPA treatment includes activation of regulatory pathways that enhance neurogenesis and suppress gliogenesis. Genes which encode the transcription factors (TFs) that specify neuronal cell fate, including MEF2D, MYT1L, NEUROD1, PAX6 and TBR1, and their target genes, are induced by VPA. VPA represses genes responsible for oligodendrogenesis, maintenance of white matter, T-cell activation, angiogenesis, and endothelial cell proliferation, adhesion and chemotaxis. NEUROD1 has regulatory interactions with 38% of the genes regulated by VPA in a swine model of TBI and HS in adult brain. Hi-C spatial mapping of a VPA pharmacogenomic SNP in the GRIN2B gene shows it is part of a transcriptional hub that contacts 12 genes that mediate chromatin-mediated neurogenesis and neuroplasticity. Following TBI and HS, this study shows that VPA administration acts in the adult brain through differential activation of TFs responsible for neurogenesis, genes responsible for neuroplasticity, and repression of TFs that specify oligodendrocyte cell fate, endothelial cell chemotaxis and angiogenesis. Short title: Mechanism of action of valproic acid in traumatic brain injury. |
X Demographics
The data shown below were collected from the profiles of 14 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 | 7 | 50% |
| United Kingdom | 1 | 7% |
| Unknown | 6 | 43% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 8 | 57% |
| Practitioners (doctors, other healthcare professionals) | 5 | 36% |
| Scientists | 1 | 7% |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 44 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 14% |
| Other | 6 | 14% |
| Student > Bachelor | 5 | 11% |
| Researcher | 5 | 11% |
| Student > Doctoral Student | 4 | 9% |
| Other | 8 | 18% |
| Unknown | 10 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 8 | 18% |
| Medicine and Dentistry | 7 | 16% |
| Biochemistry, Genetics and Molecular Biology | 7 | 16% |
| Agricultural and Biological Sciences | 4 | 9% |
| Computer Science | 2 | 5% |
| Other | 7 | 16% |
| Unknown | 9 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 12. 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 20 January 2022.
All research outputs
#3,077,926
of 25,263,619 outputs
Outputs from Pharmaceutical Research
#178
of 2,994 outputs
Outputs of similar age
#53,633
of 314,175 outputs
Outputs of similar age from Pharmaceutical Research
#5
of 32 outputs
Altmetric has tracked 25,263,619 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,994 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one has done particularly well, scoring higher than 94% of its peers.
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We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.