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Regulation of PGE2 Pathway During Cerebral Ischemia Reperfusion Injury in Rat

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Abstract

Stroke is an acute central nervous system disease with high morbidity and mortality rate. Cerebral ischemia reperfusion (I/R) injury is easily induced during the development or treatment of stroke and subsequently leads to more serious brain damage. Prostaglandin E2 (PGE2) is one of the most important inflammatory mediators in the brain and contributes to both physiological and pathophysiological functions. It may be upregulated and subsequently plays a key role in cerebral ischemia reperfusion injury. The synthesis and degradation of PGE2 is an extremely complex process, with multiple key stages and molecules. However, there are few comprehensive and systematic studies conducted to investigate the synthesis and degradation of PGE2 during cerebral I/R injury, which is what we want to demonstrate. In this study, qRT-PCR and immunoblotting demonstrated that the key enzymes in PGE2 synthesis, including COX-1, COX-2, mPGES-1 and mPGES-2, were upregulated during cerebral I/R injury, but 15-PGDH, the main PGE2 degradation enzyme, was downregulated. In addition, two of PGE2 receptors, EP3 and EP4, were also increased. Meanwhile, immunohistochemistry demonstrated the localization of these molecules in ischemic areas, including cortex, striatum and hippocampus, and reflected their expression patterns in different regions. Combining the results of PCR, Western blotting and immunohistochemistry, we can determine where the increase or decrease of these molecules occurs. Overall, these results further indicate a possible pathway that mediates enhanced production of PGE2, and thus that may impact production of inflammatory cytokines including IL-1β and TNF-α during cerebral I/R injury.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81571880, 81373147, 30901555, 30972870, 81360080, 81671895, 81471897 and 81671895) and Natural Science Foundation of Hunan Province (No. 2016JJ2157). All the funding bodies funded in the study design, collection, analysis, interpretation of data and writing the manuscript.

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  1. Yunfei Xu and Ying Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathophysiology, **angya School of Medicine, Central South University, Changsha, 410008, Hunan, China

    Yunfei Xu, Ying Liu, Kexin Li, Caihong Lv & Chunjiang Wang

  2. Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, 410008, Hunan, China

    Yunfei Xu, Ying Liu, Kexin Li, Caihong Lv & Chunjiang Wang

  3. Department of Neurosurgery, **angya Hospital, Central South University, Changsha, 410008, Hunan, China

    Jie Zhao

  4. Department of Pathology, Nan**g Drum Tower Hospital, Nan**g University Medical School, Nan**g, 210008, Jiangsu, China

    Shuying Miao

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  1. Yunfei Xu
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Contributions

YL and JZ designed and directed the project. YX and KL performed the experiments. YX, YL, KL, SM, CL and CW analyzed the data. All authors discussed the results and contributed to the final manuscript. Yunfei Xu wrote the manuscript.

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Correspondence to Ying Liu or Jie Zhao.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted by Experimental Animal Center of Central South University (Changsha, China), No: 2018sydw0222.

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Xu, Y., Liu, Y., Li, K. et al. Regulation of PGE2 Pathway During Cerebral Ischemia Reperfusion Injury in Rat. Cell Mol Neurobiol 41, 1483–1496 (2021). https://doi.org/10.1007/s10571-020-00911-5

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