• Dongmei Jin, Zhushan Dai, Lili Zhao, Tongyao Ma, Yanru Ma, and Zhongxu Zhang.
• Department of Neonatology, the First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. Electronic address: 600440@hrbmu.edu.cn.
• Neuroscience. 2024 Aug 6; 552: 546454-64.

AbstractThe activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in astrocytes has been found in the hypoxic-ischemic brain damage (HIBD) model. Cysteine rich angiogenic inducer 61 (CYR61) is secreted by reactive astrocytes. However, the effects of CYR61 on HIBD and its related mechanisms remain unclear. This study sought to explore the role of CYR61 in the activation of astrocytes and the NLRP3 inflammasome in neonatal HIBD. HIBD models were established in 7-day Sprague-Dawley rat pups. Neurobehavioral evaluation and 2,3,5-triphenyl-tetrazolium chloride staining were performed. In addition, rat primary astrocytes were used to establish the cell model of HIBD in vitro by oxygen-glucose deprivation/reperfusion (OGD/R). Then, CYR61-overexpression and sh-CYR61 viruses mediated by lentivirus were transduced into ODG/R-treated primary astrocytes. The expressions of related genes were evaluated using real-time quantitative PCR, western blot, immunofluorescence staining, and Enzyme-linked immunosorbent assay. The results showed that hypoxia-ischemia induced short-term neurological deficits, neuronal damage, and cerebral infarction in neonatal rats. In vivo, the expressions of CYR61, NLRP3, and glial fibrillary acidic protein (GFAP) were up-regulated in the HIBD model. In vitro, CYR61 exhibited high expression. CYR61 overexpression increased the expressions of GFAP and C3, whereas decreased S100A10 expression. CYR61 overexpression increased the expression of NLRP3, ASC, caspase-1 p20 and IL-1β. CYR61 overexpression activated NF-κB by promoting the phosphorylation of IκBα and p65. Thus, CYR61 is involved in neonatal HIBD progress, which may be related to the activation of astrocytes, the NLRP3 inflammasome, and the NF-κB signaling pathway.Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.

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