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• W2962850107 abstract "Abstract Aim Experimental studies have shown that the progesterone metabolite, allopregnanolone, is endowed with promyelinating effects. The mechanisms underlying these promyelinating effects are not well understood. Therefore, we explored the impact of allopregnanolone's synthetic analogue, ganaxolone, on remyelination and microglial activation following focal demyelination in the corpus callosum of ovariectomized rats. Methods Ovariectomized adult Sprague Dawley rats received a stereotaxic injection of 2 µL of 1% lysolecithin solution in the corpus callosum followed by daily injections of either ganaxolone (intraperitoneal injection [i.p.], 2.5 mg/kg) or vehicle. The demyelination lesion was assessed 3 and 7 days postdemyelination insult using Luxol fast blue staining and transmission electron microscopy. The expression levels of myelin proteins (MBP, MAG, MOG, CNPase) were explored using Western blot. The inflammatory response and clearance of damaged myelin were evaluated using immunofluorescent staining (Iba1, dMBP, GFAP) and multiplex enzyme‐linked immunosorbent assay (IL‐1β, TNF‐α, IL‐4, IL‐10, IL‐6). Results Systemic administration of ganaxolone promoted remyelination of lysolecithin‐induced demyelination, upregulated the expression of major myelin proteins, and enhanced microglial clearance of damaged myelin. Astrocytosis, as well as locally produced pro‐ and antiinflammatory cytokines, was not affected by ganaxolone treatment. Conclusion Ganaxolone promotes remyelination in response to focal demyelination of the corpus callosum of ovariectomized rats. This effect is, at least in part, mediated by enhancing microglial clearance of myelin debris, which creates a conducive environment for a successful remyelination process." @default.
• W2962850107 created "2019-07-30" @default.
• W2962850107 creator A5072230359 @default.
• W2962850107 creator A5078941490 @default.
• W2962850107 date "2019-07-22" @default.
• W2962850107 modified "2023-10-01" @default.
• W2962850107 title "Ganaxolone enhances microglial clearance activity and promotes remyelination in focal demyelination in the<i>corpus callosum</i>of ovariectomized rats" @default.
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• W2962850107 doi "https://doi.org/10.1111/cns.13195" @default.
• W2962850107 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6978248" @default.
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