Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis
Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.neures.2007.08.014
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发表时间：
2007-12-01
影响因子：
2.9
通讯作者：
Harada, Takayuki
中科院分区：
文献类型：
--
作者：
Guo, Xiaoli;Nakamura, Kazuaki;Harada, Takayuki
活化的小胶质细胞和星形胶质细胞与多发性硬化（MS）及其动物模型：实验性自身免疫性脑脊髓炎（EAE）的过程有关。MW 01 -5- 188 WH是一种选择性抑制中枢神经系统（CNS）胶质细胞活化的新药。我们在这里报告，MW 01 -5- 188 WH是有效的改善髓鞘少突胶质细胞糖蛋白（MOG）诱导的EAE的严重程度。每日经口给予5 mg/kg体重的MW 01 -5- 188 WH可降低EAE小鼠的临床评分，但对疾病发生率或动物死亡率无影响。病理学检查显示MW 01 -5- 188 WH处理的EAE小鼠脊髓中的小胶质细胞和星形胶质细胞数量减少。此外，MW 01 -5- 188 WH抑制了从培养的小胶质细胞和星形胶质细胞释放参与MS病理学的关键趋化因子。综上所述，我们的研究结果表明，抑制小胶质细胞和星形胶质细胞的激活的治疗方法应在未来的研究中寻求其作为MS治疗途径的潜力。（C）2007 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Activated microglia and astrocytes have been implicated in the course of multiple sclerosis (MS) and its animal model: experimental autoimmune encephalomyelitis (EAE). MW01-5-188WH is a novel drug that selectively inhibits glial activation in the central nervous system (CNS). We report here that MW01-5-188WH is effective to ameliorate the severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Daily oral administration of MW01-5-188WH at 5 mg/kg body weight reduced the clinical scores of EAE mice while having no influence on the disease incidence or animal mortality. Pathological examination revealed reduced numbers of microglia and astrocytes in the spinal cord of MW01-5-188WH-treated EAE mice. Moreover, MW01-5-188WH suppressed the release of key chemokines, which are involved in MS pathology, from cultured microglia and astrocytes. Taken together, our results indicate that treatments that suppress the activation of microglia and astrocytes should be pursued in future research for their potential as avenues for the treatment of MS. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.