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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury

Authors: Zhe Gong, Jingrui Pan, Qingyu Shen, Mei Li, Ying Peng

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Nod-like receptor protein 3 (NLRP3) inflammasome is a crucial factor in mediating inflammatory responses after cerebral ischemia/reperfusion (I/R), but the cellular location of NLRP3 inflammasome in cerebral I/R has yet come to a conclusion, and there is still no specific evidence to state the relationship between mitochondria and the NLRP3 inflammasome in cerebral I/R.

Methods

In the present study, we detected the cellular localization of NLRP3 inflammasomes in a transient middle cerebral artery occlusion (tMCAO) rat model and a transwell co-culture cell system under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Then, we investigated the relationship between mitochondrial dysfunction and the activation of NLRP3 inflammasomes in different cell types after OGD/R and cerebral I/R injury.

Results

Our results showed that NLRP3 inflammasomes were first activated in microglia soon after cerebral I/R injury onset and then were expressed in neurons and microvascular endothelial cells later, but they were mainly in neurons. Furthermore, mitochondrial dysfunction played an important role in activating NLRP3 inflammasomes in microglia after OGD/R, and mitochondrial protector could inhibit the activation of NLRP3 inflammasomes in cerebral I/R rats.

Conclusion

Our findings may provide novel insights into the cell type-dependent activation of NLRP3 inflammasomes at different stages of cerebral I/R injury and the role of mitochondrial dysfunction in activating the NLRP3 inflammasome pathway.
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Metadata
Title
Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury
Authors
Zhe Gong
Jingrui Pan
Qingyu Shen
Mei Li
Ying Peng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1282-6

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