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.

中文翻译：

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Ganaxolone增强去卵巢大鼠rats体局灶性脱髓鞘中的小胶质细胞清除活性并促进髓鞘再生。

目的AIM实验研究表明，孕酮代谢产物allopregnanolone具有促髓鞘作用。这些早髓作用的机制尚不清楚。因此，我们探讨了去甲肾上腺切除后的focal体局灶性脱髓鞘后，Allopregnanolone的合成类似物ganaxolone对髓鞘再生和小胶质细胞活化的影响。方法卵巢切除的成年Sprague Dawley大鼠在call体中接受立体定位注射2 µL 1％溶血卵磷脂溶液，然后每日注射ganaxolone（腹膜内注射[ip]，2.5 mg / kg）或溶媒。脱髓鞘损伤后第3天和第7天使用Luxol快速蓝染色和透射电子显微镜对脱髓鞘病变进行评估。使用蛋白质印迹探索髓磷脂蛋白（MBP，MAG，MOG，CNPase）的表达水平。使用免疫荧光染色（Iba1，dMBP，GFAP）和多重酶联免疫吸附测定（IL-1β，TNF-α，IL-4，IL-10，IL-6）评估炎症反应和受损髓鞘的清除。结果全身服用ganaxolone可以促进溶血卵磷脂诱导的脱髓鞘的髓鞘再生，上调主要髓鞘蛋白的表达，并增强受损髓鞘的小胶质细胞清除率。星形胶质细胞增多症以及局部产生的促炎和抗炎细胞因子不受加纳索龙治疗的影响。结论Ganaxolone响应去卵巢大鼠rats体局灶性脱髓鞘反应而促进髓鞘再生。这种影响至少部分是，