Maternal Inflammation Exaggerates Offspring Susceptibility to Cerebral Ischemia-Reperfusion Injury via the COX-2/PGD2/DP2 Pathway Activation

作者全名："Li, Yuke; Luo, Wen; Zhang, Jiahua; Luo, Ying; Han, Wenli; Wang, Hong; Xia, Hui; Chen, Zhihao; Yang, Yang; Chen, Qi; Li, Huan; Yang, Lu; Hu, Congli; Huang, Haifeng; Peng, Zhe; Tan, Xiaodan; Li, Miaomiao; Yang, Junqing"

作者地址："[Li, Yuke; Zhang, Jiahua; Luo, Ying; Wang, Hong; Xia, Hui; Chen, Zhihao; Yang, Yang; Li, Huan; Yang, Lu; Hu, Congli; Huang, Haifeng; Peng, Zhe; Tan, Xiaodan; Li, Miaomiao; Yang, Junqing] Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Luo, Wen] Third Hosp Mianyang, Sichuan Mental Hlth Ctr, Dept Clin Pharm, Mianyang 621000, Sichuan, Peoples R China; [Han, Wenli] Chongqing Med Univ, Lab Anim Ctr, Chongqing 400016, Peoples R China; [Chen, Qi] Pharm Dept Guizhou Prov Peoples Hosp, Guiyang 550000, Guizhou, Peoples R China"

通信作者："Yang, JQ (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China."

来源：OXIDATIVE MEDICINE AND CELLULAR LONGEVITY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000789453100002

JCR分区：Q2

影响因子：7.31

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The pathogenesis of cerebral ischemia-reperfusion (I/R) injury is complex and does not exhibit an effective strategy. Maternal inflammation represents one of the most important factors involved in the etiology of brain injury in newborns. We aimed to investigate the effect of maternal inflammation on offspring susceptibility to cerebral I/R injury and the mechanisms by which it exerts its effects. Pregnant SD rats were intraperitoneally injected with LPS (300 mu g/kg/day) at gestational days 11, 14, and 18. Pups were subjected to MCAO/R on postnatal day 60. Primary neurons were obtained from postnatal day 0 SD rats and subjected to OGD/R. Neurological deficits, brain injury, neuronal viability, neuronal damage, and neuronal apoptosis were assessed. Oxidative stress and inflammation were evaluated, and the expression levels of COX-2/PGD2/DP pathway-related proteins and apoptotic proteins were detected. Maternal LPS exposure significantly increased the levels of oxidative stress and inflammation, significantly activated the COX-2/PGD2/DP2 pathway, and increased proapoptotic protein expression. However, maternal LPS exposure significantly decreased the antiapoptotic protein expression, which subsequently increased neurological deficits and cerebral I/R injury in offspring rats. The corresponding results were observed in primary neurons. Moreover, these effects of maternal LPS exposure were reversed by a COX-2 inhibitor and DP1 agonist but exacerbated by a DP2 agonist. In conclusion, maternal inflammatory exposure may increase offspring susceptibility to cerebral I/R injury. Moreover, the underlying mechanism might be related to the activation of the COX-2/PGD2/DP2 pathway. These findings provide a theoretical foundation for the development of therapeutic drugs for cerebral I/R injury."

基金机构：Natural Science Foundation of China [81070972]

基金资助正文：We give special Thanks are due to "Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology" for providing the technical support and experimental platform. This study was supported by grants from the Natural Science Foundation of China (81070972 to Junqing Yang).