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Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia

Overview of attention for article published in Journal of Neuroinflammation, March 2016
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Title
Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia
Published in
Journal of Neuroinflammation, March 2016
DOI 10.1186/s12974-016-0528-4
Pubmed ID
Authors

Ting-Ting Song, Yan-Hua Bi, Yu-Qi Gao, Rui Huang, Ke Hao, Gang Xu, Jia-Wei Tang, Zhi-Qiang Ma, Fan-Ping Kong, John H. Coote, Xue-Qun Chen, Ji-Zeng Du

Abstract

High-altitude cerebral edema (HACE) is the severe type of acute mountain sickness (AMS) and life threatening. A subclinical inflammation has been speculated, but the exact mechanisms underlying the HACE are not fully understood. Human volunteers ascended to high altitude (3860 m, 2 days), and rats were exposed to hypoxia in a hypobaric chamber (5000 m, 2 days). Human acute mountain sickness was evaluated by the Lake Louise Score (LLS), and plasma corticotrophin-releasing hormone (CRH) and cytokines TNF-α, IL-1β, and IL-6 were measured in rats and humans. Subsequently, rats were pre-treated with lipopolysaccharide (LPS, intraperitoneal (ip) 4 mg/kg, 11 h) to induce inflammation prior to 1 h hypoxia (7000 m elevation). TNF-α, IL-1β, IL-6, nitric oxide (NO), CRH, and aquaporin-4 (AQP4) and their gene expression, Evans blue, Na(+)-K(+)-ATPase activity, p65 translocation, and cell swelling were measured in brain by ELISA, Western blotting, Q-PCR, RT-PCR, immunohistochemistry, and transmission electron micrography. MAPKs, NF-κB pathway, and water permeability of primary astrocytes were demonstrated. All measurements were performed with or without LPS challenge. The release of NO, TNF-α, and IL-6 in cultured primary microglia by CRH stimulation with or without PDTC (NF-κB inhibitor) or CP154,526 (CRHR1 antagonist) were measured. Hypobaric hypoxia enhanced plasma TNF-α, IL-1β, and IL-6 and CRH levels in human and rats, which positively correlated with AMS. A single LPS injection (ip, 4 mg/kg, 12 h) into rats increased TNF-α and IL-1β levels in the serum and cortex, and AQP4 and AQP4 mRNA expression in cortex and astrocytes, and astrocyte water permeability but did not cause brain edema. However, LPS treatment 11 h prior to 1 h hypoxia (elevation, 7000 m) challenge caused cerebral edema, which was associated with activation of NF-κB and MAPKs, hypoxia-reduced Na(+)-K(+)-ATPase activity and blood-brain barrier (BBB) disruption. Both LPS and CRH stimulated TNF-α, IL-6, and NO release in cultured rat microglia via NF-κB and cAMP/PKA. Preexisting systemic inflammation plus a short severe hypoxia elicits cerebral edema through upregulated AQP4 and water permeability by TLR4 and CRH/CRHR1 signaling. This study revealed that both infection and hypoxia can cause inflammatory response in the brain. Systemic inflammation can facilitate onset of hypoxic cerebral edema through interaction of astrocyte and microglia by activation of TLR4 and CRH/CRHR1 signaling. Anti-inflammatory agents and CRHR1 antagonist may be useful for prevention and treatment of AMS and HACE.

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X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 1 1%
Unknown 66 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 22%
Researcher 10 15%
Student > Bachelor 8 12%
Student > Master 6 9%
Student > Doctoral Student 3 4%
Other 11 16%
Unknown 14 21%
Readers by discipline Count As %
Medicine and Dentistry 14 21%
Agricultural and Biological Sciences 12 18%
Biochemistry, Genetics and Molecular Biology 10 15%
Neuroscience 6 9%
Psychology 2 3%
Other 6 9%
Unknown 17 25%
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 13 March 2016.
All research outputs
#18,447,592
of 22,856,968 outputs
Outputs from Journal of Neuroinflammation
#2,075
of 2,642 outputs
Outputs of similar age
#218,049
of 299,532 outputs
Outputs of similar age from Journal of Neuroinflammation
#34
of 41 outputs
Altmetric has tracked 22,856,968 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,642 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 12th percentile – i.e., 12% of its peers scored the same or lower than it.
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 299,532 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one is in the 4th percentile – i.e., 4% of its contemporaries scored the same or lower than it.