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Experimental Brain Research
Published in: Experimental Brain Research 6/2024

02-04-2024 | Cerebral Small Vessel Disease | Research Article

Activation of NLRP3 inflammasome in a rat model of cerebral small vessel disease

Authors: Meiyan Zhang, Xiaoyan Lan, Yue Gao, Yu Zou, Shen Li, Yajie Liang, Miroslaw Janowski, Piotr Walczak, Chengyan Chu

Published in: Experimental Brain Research | Issue 6/2024

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Abstract

Cerebral small vessel disease (CSVD) is increasingly being recognized as a leading contributor to cognitive impairment in the elderly. However, there is a lack of effective preventative or therapeutic options for CSVD. In this exploratory study, we investigated the interplay between neuroinflammation and CSVD pathogenesis as well as the cognitive performance, focusing on NLRP3 signaling as a new therapeutic target. Spontaneously hypertensive stroke-prone (SHRSP) rats served as a CSVD model. We found that SHRSP rats showed decline in learning and memory abilities using morris water maze test. Activated NLRP3 signaling and an increased expression of the downstream pro-inflammatory factors, including IL (interleukin)-6 and tumor necrosis factor α were determined. We also observed a remarkable increase in the production of pyroptosis executive protein gasdermin D, and elevated astrocytic and microglial activation. In addition, we identify several neuropathological hallmarks of CSVD, including blood-brain barrier breakdown, white matter damage, and endothelial dysfunction. These results were in correlation with the activation of NLRP3 inflammasome. Thus, our findings reveal that the NLRP3-mediated inflammatory pathway could play a central role in the pathogenesis of CSVD, presenting a novel target for potential CSVD treatment.
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Metadata
Title
Activation of NLRP3 inflammasome in a rat model of cerebral small vessel disease
Authors
Meiyan Zhang
Xiaoyan Lan
Yue Gao
Yu Zou
Shen Li
Yajie Liang
Miroslaw Janowski
Piotr Walczak
Chengyan Chu
Publication date
02-04-2024
Publisher
Springer Berlin Heidelberg
Published in
Experimental Brain Research / Issue 6/2024
Print ISSN: 0014-4819
Electronic ISSN: 1432-1106
DOI
https://doi.org/10.1007/s00221-024-06824-9

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