Dipartimento di Scienze Farmacologiche e Biomolecolari-Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
J Neuroimmune Pharmacol. 2013 Mar;8(1):238-50. doi: 10.1007/s11481-012-9385-9. Epub 2012 Jun 30.
Different experimental autoimmune encephalomyelitis models (EAE) have been developed. However, due to the different experimental conditions applied, observations simultaneously considering different pathological targets are still scarce. Using EAE induced in Dark Agouti rats with syngenic whole spinal cord homogenate suspended in incomplete Freund's adjuvant, we here analyze neurosteroidogenic machinery, cytokine levels, microglial cells, infiltration of inflammatory cells, myelin proteins and Na(+), K(+)-ATPase pump activity in the spinal cord. Data obtained in the acute phase of the disease confirmed that neurological signs were accompanied by the presence of perivascular infiltrating T cells (CD3(+) cells) and activated monocytic/microglial cells (ED1(+) and MHC-II(+)) in the spinal cord. In particular, the number of MHC-II(+) cells was significantly increased in association with increased expression of pro- (i.e., TNF-α, IL-1β) and anti-inflammatory (i.e., TGF-β) cytokines as well as with decreased expression of proteolipid protein and myelin basic protein. During the chronic phase of the disease, the number of MHC-II(+) cells was still increased, although less than in the acute phase. Changes in the number of MHC-II(+) cells were associated with decreased Na(+),K(+)-ATPase enzymatic activity. A general decrease in the levels of neuroactive steroids, with the exception of an increase in tetrahydroprogesterone and 17β-estradiol, was detected in the acute phase. These changes were maintained or reverted in the chronic phase of EAE. In conclusion, we report that modifications in the neuroimmune response in the acute and chronic phases of EAE are associated with specific changes in myelin proteins, Na(+),K(+)-ATPase pump and in the levels of neuroactive steroids.
已建立了不同的实验性自身免疫性脑脊髓炎（EAE）模型。然而，由于应用的实验条件不同，同时观察不同的病理靶标仍然很少。我们使用 Dark Agouti 大鼠中用同种全脊髓匀浆悬浮于不完全弗氏佐剂诱导的 EAE 模型，在此分析神经甾体生成机制、细胞因子水平、小胶质细胞、炎症细胞浸润、髓鞘蛋白和 Na+，K+-ATP 酶泵活性在脊髓中。疾病急性期获得的数据证实，神经症状伴随着血管周围浸润的 T 细胞（CD3+细胞）和活化的单核/小胶质细胞（ED1+和 MHC-II+）在脊髓中的存在。特别是，MHC-II+细胞的数量显著增加，与促炎（即 TNF-α，IL-1β）和抗炎（即 TGF-β）细胞因子的表达增加以及蛋白脂质蛋白和髓鞘碱性蛋白的表达减少有关。在疾病的慢性期，MHC-II+细胞的数量仍然增加，尽管少于急性期。MHC-II+细胞数量的变化与 Na+，K+-ATP 酶酶活性降低有关。在急性期检测到神经活性甾体水平普遍降低，除四氢孕酮和 17β-雌二醇增加外。这些变化在 EAE 的慢性期得以维持或逆转。总之，我们报告说，EAE 急性期和慢性期神经免疫反应的改变与髓鞘蛋白、Na+，K+-ATP 酶泵和神经活性甾体水平的特定变化有关。
