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This work aims were to assess if golexanolone affords sustained improvement of glial activation and pro-inflammatory factors at 3 and 9 weeks after 6-OHDA injection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>6-OHDA rats show pro-inflammatory microglia in SN and striatum, with reduced area and increased TNF\u03b1 at 3 and 9 weeks, increased TNF\u03b1, IL-1\u03b1 and HMGB1 and pro-inflammatory A1 astrocytes activation with increased GFAP, vimentin and S100B and reduced S100A10. Golexanolone reversed microglia activation, the increase in pro-inflammatory factors and astrocytes A1 activation both at 3 and 9 weeks. Golexanolone reversed microglia activation, the increase in pro-inflammatory factors and astrocytes A1 activation both at 3 and 9 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Sustained improvement of glial activation in SN and striatum would be a key mechanism in the improvement of PD symptoms by golexanolone.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1654664","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T04:14:40Z","timestamp":1756872880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Golexanolone affords sustained microglia and astrocytes activation improvement in a rat model of Parkinson\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Gergana","family":"Mincheva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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