Purpose

To investigate the brain protective effects of fingolimod on inflammatory response of SAH mice.

Methods

We utilized an endovascular mouse perforation model of SAH. Mice were divided into three groups: sham group, SAH group and SAH + Fingolimod group. Mice received either saline or fingolimod (1 mg/kg) intraperitoneally 2 h after sham surgery or SAH. The modified neurological severity score (mNSS) and Morris water maze were respectively used to evaluate the influence of nerve function. Evens blue (EB) extravasation was used to detect the permeability of blood-brain barrier, and water content in brain tissue was also detected. Flow cytometry, ELISA kits and western blotting were used to detect inflammatory factors in brain tissue.

Results

The results showed that compared with SAH group, after treatment, the delay time of locating the hidden platform was shorter. The mNSS results showed that fingolimod improved the behavior of SAH mice. In addition, fingolimod could reduce the water content in brain. Flow cytometry results showed that after 3 d of treatment, fingolimod significantly increased Treg cells and down-regulated NK cells. Western blotting results showed fingolimod inhibited the expression of inflammatory cytokines in brain tissue. ELISA kit results showed that fingolimod could down-regulate IL-6 and TNF-α and up-regulate IL-10 and TGF-β1 in serum.

Conclusions

Fingolimod could regulate the inflammatory response to alleviate SAH-induced brain damage and promote neurological recovery, which provides a new therapeutic strategy for SAH treatment.

中文翻译：

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芬戈莫德给药可改善蛛网膜下腔出血小鼠的神经功能。

目的

研究芬戈莫德对SAH小鼠炎症反应的脑保护作用。

方法

我们利用了SAH的血管内小鼠穿孔模型。将小鼠分为三组：假手术组，SAH组和SAH +芬戈莫德组。假手术或SAH后2小时，腹膜内给予小鼠盐水或芬戈莫德（1 mg / kg）。修改后的神经系统严重程度评分（mNSS）和莫里斯水迷宫分别用于评估神经功能的影响。偶数蓝色（EB）外渗用于检测血脑屏障的通透性，并且还检测脑组织中的水分。流式细胞仪，ELISA试剂盒和蛋白质印迹法被用于检测脑组织中的炎症因子。

结果

结果表明，与SAH组相比，治疗后隐蔽平台定位延迟时间短。mNSS结果表明芬戈莫德改善了SAH小鼠的行为。此外，芬戈莫德还可以降低大脑中的水分含量。流式细胞仪结果显示，治疗3天后，芬戈莫德显着增加Treg细胞和下调NK细胞。蛋白质印迹结果表明芬戈莫德抑制了脑组织中炎性细胞因子的表达。ELISA试剂盒检测结果显示，芬戈莫德可以下调血清中IL-6和TNF-α，上调IL-10和TGF-β1。

结论

芬戈莫德可以调节炎症反应，减轻SAH诱导的脑损伤，促进神经功能恢复，为SAH治疗提供了新的治疗策略。