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拉喹莫德口服治疗增强了实验性自身免疫性脑脊髓炎小鼠中枢神经系统中调节性 T 细胞和脑源性神经营养因子的表达,并减轻了损伤。

Oral treatment with laquinimod augments regulatory T-cells and brain-derived neurotrophic factor expression and reduces injury in the CNS of mice with experimental autoimmune encephalomyelitis.

机构信息

Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

出版信息

J Neuroimmunol. 2012 Oct 15;251(1-2):14-24. doi: 10.1016/j.jneuroim.2012.06.005. Epub 2012 Jun 28.

Abstract

Laquinimod is an orally active molecule that showed efficacy in clinical trials in multiple sclerosis. We studied its effects in the CNS, when administered by therapeutic regimen to mice inflicted with experimental autoimmune encephalomyelitis (EAE). Laquinimod reduced clinical and inflammatory manifestations and elevated the prevalence of T-regulatory cells in the brain. In untreated mice, in the chronic disease stage, brain derived neurotrophic factor (BDNF) expression was impaired. Laquinimod treatment restored BDNF expression to its level in healthy controls. Furthermore, CNS injury, manifested by astrogliosis, demyelination and axonal damages, was significantly reduced following laquinimod treatment, indicating its immunomodulatory and neuroprotective activity.

摘要

拉喹莫德是一种具有口服活性的分子,在多发性硬化症的临床试验中显示出疗效。我们研究了它在中枢神经系统中的作用,当通过治疗方案给予患有实验性自身免疫性脑脊髓炎 (EAE) 的小鼠时。拉喹莫德减少了临床和炎症表现,并增加了大脑中 T 调节细胞的流行率。在未经治疗的小鼠中,在慢性疾病阶段,脑源性神经营养因子 (BDNF) 的表达受损。拉喹莫德治疗将 BDNF 的表达恢复到健康对照组的水平。此外,神经胶质增生、脱髓鞘和轴突损伤等中枢神经系统损伤在拉喹莫德治疗后显著减少,表明其具有免疫调节和神经保护活性。

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