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Cerebral Ischemia-Reperfusion Injury: Lysophosphatidic Acid Mediates Inflammation by Decreasing the Expression of Liver X Receptor

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Abstract

Lysophosphatidic acid (LPA), a ubiquitous phospholipid, plays a crucial role in the pathogenesis and pathophysiological process of neurological diseases, which constitute the pathological course after cerebral ischemia. Nevertheless, the molecular mechanisms associated with the pathogenic roles of LPA remain elusive. In this study, we evaluated the expression of the liver X receptor (LXR) and nuclear factor kappa B (NFκB) by Western blotting, quantified the levels of IL-1β, IL-6, TNF-α, and LPA by ELISA, and evaluated apoptosis and infarct by TUNEL (terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling) and TTC (triphenyltetrazolium chloride) staining respectively in Sprague-Dawley (SD) rats after middle cerebral artery occlusion (MCAO). The levels of LPA, an extracellular signaling molecule, increased after ischemia and caused neurological injury effect, decreased the expression level of LXR, and increased the expression level of inflammatory factors (IL-1β, IL-6, and TNF-α) via the NFκB signaling pathway. This elevated LPA-induced pathological process is one of the pathological reactions associated with ischemic brain injury. We present a direct or indirect connection between LPA and LXR in the pathophysiological process. In conclusion, we speculate that the inhibition of LPA generation and administration of LXR agonist may be explored as potential cerebral infarction treatment strategies.

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Funding

This study was financially supported by the Hubei Province Health and Family Planning Scientific Research Project to Xiaoyun Zeng (WJ2019M021).

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Authors and Affiliations

  1. Department of Neurology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China

    Xiaoyun Zeng, Zhixiu Luo, Junyi Wu, Jie Zhou, Yandong Shan, Yang Zhu, Guilin Yan, Yahang Lin & Chao Wang

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  1. Xiaoyun Zeng
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  2. Zhixiu Luo
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  3. Junyi Wu
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  4. Jie Zhou
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  5. Yandong Shan
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  6. Yang Zhu
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  7. Guilin Yan
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  8. Yahang Lin
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  9. Chao Wang
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Correspondence to Chao Wang.

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Zeng, X., Luo, Z., Wu, J. et al. Cerebral Ischemia-Reperfusion Injury: Lysophosphatidic Acid Mediates Inflammation by Decreasing the Expression of Liver X Receptor. J Mol Neurosci 70, 1376–1384 (2020). https://doi.org/10.1007/s12031-020-01554-3

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  • DOI: https://doi.org/10.1007/s12031-020-01554-3

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