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Inhibition of perilipin 2 attenuates cerebral ischemia/reperfusion injury by blocking NLRP3 inflammasome activation both in vivo and in vitro

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Abstract

Cerebral ischemia/reperfusion (CI/R) usually causes neuroinflammation within the central nervous system, further prompting irreversible cerebral dysfunction. Perilipin 2 (Plin2), a lipid droplet protein, has been reported to exacerbate the pathological process in different diseases, including inflammatory responses. However, the role and mechanism of Plin2 in CI/R injury are unclear. In this study, the rat models of transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R) were established to mimic I/R injury, and we found that Plin2 was highly expressed in the ischemic penumbra of tMCAO/R rats. The siRNA-mediated knockdown of Plin2 significantly decreased neurological deficit scores and reduced infarct areas in rats induced by I/R. Detailed investigation showed that Plin2 deficiency alleviated inflammation of tMCAO/R rats as evidenced by reduced secretion of proinflammatory factors and the blockade of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. In vitro experiments showed that Plin2 expression was upregulated in mouse microglia subjected to oxygen–glucose deprivation/reoxygenation (OGD/R). Plin2 knockdown inhibited OGD/R-induced microglia activation and the accumulation of inflammation-related factors. Taken together, this study demonstrates that lipid droplet protein Plin2 contributes to the pathologic process of CI/R damage by impacting inflammatory response and NLRP3 inflammasome activation. Thus, Plin2 may provide a new therapeutic direction for CI/R injury.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81371461).

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Authors and Affiliations

  1. Medical College of Soochow University, Suzhou, Jiangsu, China

    Xu-Ying Liu

  2. Department of Neurology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China

    Xu-Ying Liu, Wen-Hai Yang, Yue Qiu, Fei-Fei Zhang, Xiu-Hui Mei & Qi-Wen Yuan

  3. Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Jinzhou, Liaoning, China

    Qiu-Shi Li & Ru-Bo Sui

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  1. Xu-Ying Liu
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Contributions

XYL and RBS conceived the study. XYL, QSL, and RBS participated in its design and coordination. XYL performed most of the experiments and analyzed the data. XYL and WHY contributed to the establishment of tMCAO/R rat models. XYL, YQ, and FFZ performed behavioral testing experiments and analyzed the data. XYL, QSL, XHM, and QWY drafted the manuscript. RBS supervised the project and edited the paper. All authors have read and approved the final manuscript.

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Correspondence to Ru-Bo Sui.

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Liu, XY., Li, QS., Yang, WH. et al. Inhibition of perilipin 2 attenuates cerebral ischemia/reperfusion injury by blocking NLRP3 inflammasome activation both in vivo and in vitro. In Vitro Cell.Dev.Biol.-Animal 59, 204–213 (2023). https://doi.org/10.1007/s11626-023-00759-1

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  • DOI: https://doi.org/10.1007/s11626-023-00759-1

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