Background. Stroke activates the immune system and induces brain infiltration by immune cells, aggravating brain injury. Poststroke immunomodulation via (S1P-)receptor modulation is beneficial; however, the S1P-modulator in clinical use (FTY-720) is unspecific, and undesirable side effects have been reported. Previously, we tested effects of a novel selective S1P-receptor modulator, Siponimod, on ICH-induced brain injury in acute stage of the disease. In the current study, we investigated whether protective effects of Siponimod, evaluated in a short-term study, will protect the brain of ICH animals at long term as well. Methods. 134 C57BL/6N mice were divided into sham and ICH-operated groups. Collagenase model of ICH was employed. ICH animals were divided into Siponimod treated and nontreated. Dose- and time-dependent effects of Siponimod were investigated. Contraplay between development of brain injury and the number of lymphocytes infiltrating the brain was investigated by forelimb placing, T-Maze test, brain water content calculation, MRI scanning, and immunostaining. Results. Depending on the therapeutic strategy, Siponimod attenuated the development of brain edema, decreased ICH-induced ventriculomegaly and improved neurological functions of animals after ICH. It was associated with less lymphocytes in the brain of ICH animals. Conclusion. Siponimod is able to decrease the brain injury and improves neurological functions of animals after ICH.

中文翻译：

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Sphingosine-1-Phosphate Receptor Modulator 减轻 ICH 后小鼠继发性脑损伤和改善神经功能。

背景。中风会激活免疫系统并诱导免疫细胞浸润脑部，加重脑损伤。通过 (S1P-) 受体调节的卒中后免疫调节是有益的；然而，临床使用的 S1P 调节剂 (FTY-720) 是非特异性的，并且已经报道了不良副作用。此前，我们测试了一种新型选择性 S1P 受体调节剂 Siponimod 对 ICH 引起的急性期脑损伤的影响。在目前的研究中，我们调查了在短期研究中评估的 Siponimod 的保护作用是否也会长期保护 ICH 动物的大脑。方法。134 只 C57BL/6N 小鼠被分为假手术组和 ICH 手术组。采用 ICH 的胶原酶模型。ICH 动物分为辛波莫德治疗和未治疗。研究了西波莫德的剂量和时间依赖性效应。通过前肢放置、T-Maze 测试、脑含水量计算、MRI 扫描和免疫染色来研究脑损伤发展与浸润脑的淋巴细胞数量之间的反作用。结果。根据治疗策略，Siponimod 可减轻脑水肿的发展，减少 ICH 引起的脑室扩大并改善 ICH 后动物的神经功能。它与 ICH 动物大脑中的淋巴细胞减少有关。结论. Siponimod 能够减少脑损伤并改善 ICH 后动物的神经功能。