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Administration of Tauroursodeoxycholic Acid Attenuates Early Brain Injury via Akt Pathway Activation

Overview of attention for article published in Frontiers in Cellular Neuroscience, July 2017
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Title
Administration of Tauroursodeoxycholic Acid Attenuates Early Brain Injury via Akt Pathway Activation
Published in
Frontiers in Cellular Neuroscience, July 2017
DOI 10.3389/fncel.2017.00193
Pubmed ID
Authors

Dongdong Sun, Gang Gu, Jianhao Wang, Yan Chai, Yueshan Fan, Mengchen Yang, Xin Xu, Weiwei Gao, Fei Li, Dongpei Yin, Shuai Zhou, Xin Chen, Jianning Zhang

Abstract

Traumatic brain injury (TBI) is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI) device. Using western blotting, we first examined TBI-induced changes in the expression levels of GRP78, an ER stress marker, p-PERK, PERK, p-eIF2a, eIF2a, ATF4, p-Akt, Akt, Pten, Bax, Bcl-2, Caspase-12 and CHOP, as well as changes in the mRNA levels of Akt, GRP78, Caspase-12 and CHOP using RT-PCR. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, and CHOP expression in neuronal cells was detected by double-immunofluorescence staining. Neurological and motor deficits were assessed by modified neurological severity scores (mNSS) and beam balance and beam walking tests, and brain water content was also assessed. Our results indicated that ER stress peaked at 72 h after TBI and that TUDCA abolished ER stress and inhibited p-PERK, p-eIF2a, ATF4, Pten, Caspase-12 and CHOP expression levels. Moreover, our results show that TUDCA also improved neurological function and alleviated brain oedema. Additionally, TUDCA increased p-Akt expression and the Bcl-2/Bax ratio. However, the administration of the Akt inhibitor MK2206 or siRNA targeting of Akt abolished the beneficial effects of TUDCA. Taken together, our results indicate that TUDCA may attenuate early brain injury via Akt pathway activation.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 28%
Researcher 4 16%
Student > Ph. D. Student 4 16%
Student > Bachelor 3 12%
Other 1 4%
Other 2 8%
Unknown 4 16%
Readers by discipline Count As %
Neuroscience 7 28%
Agricultural and Biological Sciences 4 16%
Medicine and Dentistry 3 12%
Nursing and Health Professions 1 4%
Biochemistry, Genetics and Molecular Biology 1 4%
Other 4 16%
Unknown 5 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 16 July 2017.
All research outputs
#19,939,131
of 25,375,376 outputs
Outputs from Frontiers in Cellular Neuroscience
#3,267
of 4,689 outputs
Outputs of similar age
#233,711
of 319,720 outputs
Outputs of similar age from Frontiers in Cellular Neuroscience
#72
of 96 outputs
Altmetric has tracked 25,375,376 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,689 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
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We're also able to compare this research output to 96 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.