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

Open Access 01-12-2018 | Research

Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo

Authors: Wei Liu, Yuhua Chen, Jiao Meng, Minfei Wu, Fangfang Bi, Cuicui Chang, Hua Li, Liangjun Zhang

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Traumatic brain injury (TBI) is a critical public health and socioeconomic problem throughout the world. Inflammation-induced secondary injury is one of the vital pathogenic parameters of TBI. Molecular signaling cascades of pyroptosis, a specific type of cellular necrosis, are key drivers of TBI-induced inflammation.

Methods

In this study, mice with genetically ablated caspase-1 (caspase-1−/−) were subjected to controlled cortical impact injury in vivo, and primary neuron deficient in caspase-1 through siRNA knockdown and pharmacologic inhibition was stimulated by mechanical scratch, equiaxial stretch, and LPS/ATP in vitro. We evaluated the effects of caspase-1 deficiency on neurological deficits, inflammatory factors, histopathology, cell apoptosis, and pyroptosis.

Results

During the acute post-injury period (0–48 h) in vivo, motor deficits, anti-inflammatory cytokines (TGF-β and IL-10), pro-inflammatory cytokines (IFN-γ, IL-1β, and IL-18), and blood lactate dehydrogenase (LDH), as well as pyroptosis-related proteins (caspase-1, caspase-1 fragments, caspase-11 and GSDMD), were increased. Caspase-1 was activated in the cortex of TBI mice. Inflammatory activation was more profound in injured wild-type mice than in caspase-1−/− mice. In vitro, mechanical scratch, equiaxial stretch, and LPS/ATP-induced neuron pyroptosis, apoptosis, LDH release, and increased expression of inflammatory factors. The effects of mechanical and inflammatory stress were reduced through inhibition of caspase-1 activity through siRNA knockdown and pharmacologic inhibition.

Conclusion

Collectively, these data demonstrate that pyroptosis is involved in neuroinflammation and neuronal injury after TBI, and ablation of caspase-1 inhibits TBI-induced pyroptosis. Our findings suggest that caspase-1 may be a potential target for TBI therapy.
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Metadata
Title
Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo
Authors
Wei Liu
Yuhua Chen
Jiao Meng
Minfei Wu
Fangfang Bi
Cuicui Chang
Hua Li
Liangjun Zhang
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/s12974-018-1083-y

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