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NADPH oxidases as potential pharmacological targets against increased seizure susceptibility after systemic inflammation

Overview of attention for article published in Journal of Neuroinflammation, May 2018
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Title
NADPH oxidases as potential pharmacological targets against increased seizure susceptibility after systemic inflammation
Published in
Journal of Neuroinflammation, May 2018
DOI 10.1186/s12974-018-1186-5
Pubmed ID
Authors

Wan-Yu Huang, Shankung Lin, Hsuan-Ying Chen, Ya-Ping Chen, Ting-Yu Chen, Kuei-Sen Hsu, Hung-Ming Wu

Abstract

Systemic inflammation associated with sepsis can induce neuronal hyperexcitability, leading to enhanced seizure predisposition and occurrence. Brain microglia are rapidly activated in response to systemic inflammation and, in this activated state, release multiple cytokines and signaling factors that amplify the inflammatory response and increase neuronal excitability. NADPH oxidase (NOX) enzymes promote microglial activation through the generation of reactive oxygen species (ROS), such as superoxide anion. We hypothesized that NOX isoforms, particularly NOX2, are potential targets for prevention of sepsis-associated seizures. To reduce NADPH oxidase 2-derived ROS production, mice with deficits of NOX regulatory subunit/NOX2 organizer p47phox (p47phox-/-) or NOX2 major subunit gp91phox (gp91phox-/-) were used or the NOX2-selective inhibitor diphenyleneiodonium (DPI) was used to treat wild-type (WT) mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS). Seizure susceptibility was compared among mouse groups in response to intraperitoneal injection of pentylenetetrazole (PTZ). Brain tissues were assayed for proinflammatory gene and protein expression, and immunofluorescence staining was used to estimate the proportion of activated microglia. Increased susceptibility to PTZ-induced seizures following sepsis was significantly attenuated in gp91phox-/- and p47phox-/- mice compared with WT mice. Both gp91phox-/- and p47phox-/- mice exhibited reduced microglia activation and lower brain induction of multiple proconvulsive cytokines, including TNFα, IL-1β, IL-6, and CCL2, compared with WT mice. Administration of DPI following LPS injection significantly attenuated the increased susceptibility to PTZ-induced seizures and reduced both microglia activation and brain proconvulsive cytokine concentrations compared with vehicle-treated controls. DPI also inhibited the upregulation of gp91phox transcripts following LPS injection. Our results indicate that NADPH oxidases contribute to the development of increased seizure susceptibility in mice after sepsis. Pharmacologic inhibition of NOX may be a promising therapeutic approach to reducing sepsis-associated neuroinflammation, neuronal hyperexcitability, and seizures.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 16%
Student > Ph. D. Student 4 13%
Student > Doctoral Student 3 9%
Student > Master 3 9%
Student > Bachelor 3 9%
Other 5 16%
Unknown 9 28%
Readers by discipline Count As %
Medicine and Dentistry 8 25%
Pharmacology, Toxicology and Pharmaceutical Science 4 13%
Biochemistry, Genetics and Molecular Biology 4 13%
Neuroscience 3 9%
Social Sciences 1 3%
Other 1 3%
Unknown 11 34%
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 April 2019.
All research outputs
#17,952,510
of 23,052,509 outputs
Outputs from Journal of Neuroinflammation
#1,962
of 2,659 outputs
Outputs of similar age
#235,949
of 325,559 outputs
Outputs of similar age from Journal of Neuroinflammation
#54
of 76 outputs
Altmetric has tracked 23,052,509 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,659 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 21st percentile – i.e., 21% 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 325,559 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 76 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.