Neuroprotective Effects of Progesterone in Chronic Experimental Autoimmune Encephalomyelitis
Neuroprotective Effects of Progesterone in Chronic Experimental Autoimmune Encephalomyelitis
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DOI：
10.1111/j.1365-2826.2012.02284.x
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发表时间：
2012-06-01
影响因子：
3.2
通讯作者：
Melcangi, R. C.
中科院分区：
文献类型：
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作者：
Giatti, S.;Caruso, D.;Melcangi, R. C.
迄今为止，在实验性自身免疫性脑脊髓炎（EAE）中获得的观察结果表明，孕酮（PROG）具有良好的神经保护作用。研究结果表明，这种神经活性类固醇可能是多发性硬化症（MS）的治疗工具。然而，到目前为止，PROG的疗效仅在疾病的急性期进行了测试，而众所周知，MS根据疾病的阶段表现出不同的特征。因此，我们已经评估了PROG治疗在Dark Agglutination大鼠中诱导的EAE（即显示持久复发性EAE的实验模型）中的作用。EAE诱导后45天获得的数据显示，PROG治疗对临床评分产生有益影响，证实了慢性EAE中脊髓损伤的替代参数（即反应性小胶质细胞、细胞因子水平、Na+，K+-ATP酶泵活性和髓鞘碱性蛋白表达）。PROG处理后，在脊髓中也观察到二氢孕酮和异孕烯醇酮（即两种PROG代谢物）水平的增加。总之，这些结果表明，PROG是有效的，在降低慢性EAE的严重程度，因此，可能有潜力的MS治疗。
Observations so far obtained in experimental autoimmune encephalomyelitis (EAE) have revealed the promising neuroprotective effects exerted by progesterone (PROG). The findings suggest that this neuroactive steroid may potentially represent a therapeutic tool for multiple sclerosis (MS). However, up to now, the efficacy of PROG has been only tested in the acute phase of the disease, whereas it is well known that MS expresses different features depending on the phase of the disease. Accordingly, we have evaluated the effect of PROG treatment in EAE induced in Dark Agouti rats (i.e. an experimental model showing a protracted relapsing EAE). Data obtained 45 days after EAE induction show that PROG treatment exerts a beneficial effect on clinical score, confirming surrogate parameters of spinal cord damage in chronic EAE (i.e. reactive microglia, cytokine levels, activity of the Na+,K+-ATPase pump and myelin basic protein expression). An increase of the levels of dihydroprogesterone and isopregnanolone (i.e. two PROG metabolites) was also observed in the spinal cord after PROG treatment. Taken together, these results indicate that PROG is effective in reducing the severity of chronic EAE and, consequently, may have potential with respect to MS treatment.