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Thus, alternative treatments are urgently needed. Our previous studies showed that genistein-3\u2032-sodium sulfonate (GSS), a derivative of genistein (Gen), has a strong neuroprotective effect in rats with ischaemic stroke, but its role in HIE is unclear. A hypoxia\u2013ischaemia (HI) brain injury model was established in neonatal male Sprague\u2012Dawley (SD) rats. Twenty-four hours after reperfusion, rats treated with GSS were assessed for cerebral infarction, neurological function, and neuronal damage. RNA-Seq and bioinformatics analysis were used to explore differentially expressed genes (DEGs) and regulated signalling pathways, which were subsequently validated by Western blotting and immunofluorescence. In this study, we found that GSS not only significantly reduced the size of brain infarcts and alleviated nerve damage in rats with HIE but also inhibited neuronal loss and degeneration in neonatal rats with HIE. A total of 2170 DEGs, of which 1102 were upregulated and 1068 were downregulated, were identified in the GSS group compared with the HI group. In an analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) categories, the downregulated DEGs were significantly enriched in the pathways \u201cPhagosome\u201d, \u201cNF-\u03baB signalling\u201d, and \u201cComplement and coagulation cascades\u201d, amongst others. Meanwhile, the upregulated DEGs were significantly enriched in the pathways \u201cNeurodegeneration\u201d, \u201cGlutamatergic synapse\u201d, and \u201cCalcium signalling pathway\u201d, amongst others. These results indicate that GSS intervenes in the process of HIE-induced brain injury by participating in multiple pathways, which suggests potential candidate drugs for the treatment of HIE.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s12035-022-03123-8","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T11:02:59Z","timestamp":1668250979000},"page":"807-819","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Insight into the Neuroprotective Effect of Genistein-3\u2032-Sodium Sulfonate Against Neonatal Hypoxic-Ischaemic Brain Injury in Rats by Bioinformatics"],"prefix":"10.1007","volume":"60","author":[{"given":"Ting","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Shuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaigai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2610-1999","authenticated-orcid":false,"given":"Zhihua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"issue":"6","key":"3123_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.earlhumdev","volume":"86","author":"JJ Kurinczuk","year":"2010","unstructured":"Kurinczuk JJ, White-Koning M, Badawi N (2010) Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. 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