TY -的T1 Astrocyte-derived HB-EGF促进康复中枢神经系统自身免疫性炎症和疾病是一个潜在的目标进步(p2 - 3.006) JF -神经学乔-神经学做- 10.1212 / WNL。首页0000000000202915六世- 100 - 17补充2 SP - 2954 AU -马Linnerbauer盟莉娜Loesslein AU - Thanos Tsaktanis盟Maja Jagodic AU -弗朗西斯科Quintana盟Veit Rothhammer Y1 - 2023/04/25 UR - //www.ez-admanager.com/content/100/17_Supplement_2/2954.首页abstract N2 -目的:识别小说tissue-protective因素由星形胶质细胞治疗的潜在治疗进展型多发性硬化症(MS)。背景:近年来,大量研究证明了炎性astrocyte-subsets参与神经炎症的发病机制和传播事件,在人类和动物模型。然而,它最近才变得明显,底层的异构性星形胶质细胞不仅可以驱动炎症,但也导致其决议通过直接和间接的机制。在这种背景下,单细胞的方法帮助我们理解的不断出现,这些致病和保护激活状态扩展或收缩在一个高度spatiotemporal-dependent方式。这在进行性神经炎症阶段变得特别重要,当局部炎症过程限制CNS-resident胶质细胞的再生能力,最终导致疾病的临床恶化和chronification。设计/方法:在这里,我们使用CRISPR-Cas9-based遗传扰动模型,全基因组分析皮质星形胶质细胞的DNA甲基化和新颖的治疗方法结合纵向磁共振成像(MRI)进行调查的相关性Heparin-binding EGF-like生长因子(HB-EGF)在实验性自身免疫性脑脊髓炎的上下文(运算单元),多发性硬化症的临床前小鼠模型。结果:我们确定HB-EGF作为保护的一部分,星形胶质细胞活化状态这限制了晚期中枢神经系统炎症和epigenetically沉默在进步。废除的astrocyte-derived HB-EGF导致受损的决议的中枢神经系统炎症和进步的疾病恶化,同时增加了髓鞘脱失,神经退化和持续的炎症。相比之下,鼻内交付重组HB-EGF期间急性毒晚期中枢神经系统炎症和疾病严重程度,降低病变负担和促进复苏。结论:总的来说,我们证明慢性激活星形胶质细胞epigenetically抑制保护HB-EGF信号,和现在的小说策略治疗急性和慢性中枢神经系统炎症。披露:Linnerbauer先生没有披露。Loesslein太太没有披露。 Dr. Tsaktanis has nothing to disclose. The institution of Prof. Jagodic has received research support from Swedish Research Council. The institution of Prof. Jagodic has received research support from EU Horizon 2020 (MultipleMS). The institution of Prof. Jagodic has received research support from European Research Council (ERC-CoG). Dr. Quintana has nothing to disclose. Prof. Rothhammer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Rothhammer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Prof. Rothhammer has received research support from German Research Foundation. The institution of Prof. Rothhammer has received research support from European Research Council. ER -