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Ex vivo model of epilepsy in organotypic slices—a new tool for drug screening

Overview of attention for article published in Journal of Neuroinflammation, July 2018
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Title
Ex vivo model of epilepsy in organotypic slices—a new tool for drug screening
Published in
Journal of Neuroinflammation, July 2018
DOI 10.1186/s12974-018-1225-2
Pubmed ID
Authors

Daniela M. Magalhães, Noémia Pereira, Diogo M. Rombo, Cláudia Beltrão-Cavacas, Ana M. Sebastião, Cláudia A. Valente

Abstract

Epilepsy is a prevalent neurological disorder worldwide. It is characterized by an enduring predisposition to generate seizures and its development is accompanied by alterations in many cellular processes. Organotypic slice cultures represent a multicellular environment with the potential to assess biological mechanisms, and they are used as a starting point for refining molecules for in vivo studies. Here, we investigated organotypic slice cultures as a model of epilepsy. We assessed, by electrophysiological recordings, the spontaneous activity of organotypic slices maintained under different culture protocols. Moreover, we evaluated, through molecular-based approaches, neurogenesis, neuronal death, gliosis, expression of proinflammatory cytokines, and activation of NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain) as biomarkers of neuroinflammation. We demonstrated that organotypic slices, maintained under a serum deprivation culture protocol, develop epileptic-like activity. Furthermore, throughout a comparative study with slices that do not depict any epileptiform activity, slices with epileptiform activity were found to display significant differences in terms of inflammation-related features, such as (1) increased neuronal death, with higher incidence in CA1 pyramidal neurons of the hippocampus; (2) activation of astrocytes and microglia, assessed through western blot and immunohistochemistry; (3) upregulation of proinflammatory cytokines, specifically interleukin-1β (IL-1β), interleukin-6, and tumor necrosis factor α, revealed by qPCR; and (4) enhanced expression of NLRP3, assessed by western blot, together with increased NLRP3 activation, showed by IL-1β quantification. Thus, organotypic slice cultures gradually deprived of serum mimic the epileptic-like activity, as well as the inflammatory events associated with in vivo epilepsy. This system can be considered a new tool to explore the interplay between neuroinflammation and epilepsy and to screen potential drug candidates, within the inflammatory cascades, to reduce/halt epileptogenesis.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 22%
Student > Master 10 22%
Researcher 6 13%
Other 4 9%
Student > Bachelor 3 7%
Other 5 11%
Unknown 7 16%
Readers by discipline Count As %
Neuroscience 15 33%
Biochemistry, Genetics and Molecular Biology 6 13%
Pharmacology, Toxicology and Pharmaceutical Science 5 11%
Medicine and Dentistry 4 9%
Engineering 2 4%
Other 4 9%
Unknown 9 20%

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 July 2018.
All research outputs
#11,734,762
of 13,218,736 outputs
Outputs from Journal of Neuroinflammation
#1,312
of 1,538 outputs
Outputs of similar age
#230,485
of 266,390 outputs
Outputs of similar age from Journal of Neuroinflammation
#9
of 12 outputs
Altmetric has tracked 13,218,736 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,538 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.