Department of Geriatrics, The First People's Hospital of Yancheng, The Fourth Affiliated Hospital of Nantong University, Yancheng, China.
Neurology, The First People's Hospital of Yancheng, The Fourth Affiliated Hospital of Nantong University, Yancheng, China.
Neurol India. 2022 Jul-Aug;70(4):1517-1524. doi: 10.4103/0028-3886.355128.
Cerebral vasospasm (CVS) is a major complication of subarachnoid hemorrhage (SAH). Inflammation and nitric oxide (NO) have become increasingly recognized as key pathogenic contributors to brain injury in this condition. We aimed to examine the role of FTY720 in CVS after SAH. Endovascular perforation was used to establish an SAH model. Seventy-five male Sprague-Dawley rats were randomly divided into five groups: sham, sham + FTY720, SAH + saline, and two SAH + FTY720 (0.5 and 1 mg/kg) groups. The results showed that FTY720 treatment in both the surgery and nonsurgery groups decreased the counts of leukocytes and lymphocytes 72 hours after SAH. TNF-α (tumor necrosis factor alpha) and IL-1β (interleukin 1 beta) in both the cerebrospinal fluid (CSF) and the hippocampus were decreased, and the NF-κB (nuclear factor kappa B) pathway was inhibited. The levels of apoptotic proteins were downregulated. FTY720 promoted NO generation by activating the PI3K/AKT/eNOS pathway. CVS and neurological deficits in the SAH rats were ameliorated after FTY720 treatment. Compared with the sham-only animals, FTY720 treatment in the nonsurgery group did not increase mortality. These results indicated that FTY720 could alleviate CVS due to its anti-inflammatory and antiapoptosis effects and the promotion of NO generation. FTY720 may be effective in the clinical treatment of SAH patients.
脑血管痉挛（CVS）是蛛网膜下腔出血（SAH）的主要并发症。在这种情况下，炎症和一氧化氮（NO）已被越来越多地认为是导致脑损伤的关键致病因素。我们旨在研究 FTY720 在 SAH 后 CVS 中的作用。血管内穿孔用于建立 SAH 模型。75 只雄性 Sprague-Dawley 大鼠随机分为五组：假手术组、假手术+FTY720 组、SAH+盐水组和两种 SAH+FTY720（0.5 和 1mg/kg）组。结果表明，FTY720 治疗在手术和非手术组中，均使 SAH 后 72 小时白细胞和淋巴细胞计数减少。脑脊液（CSF）和海马中的 TNF-α（肿瘤坏死因子 alpha）和 IL-1β（白细胞介素 1 beta）减少，NF-κB（核因子 kappa B）途径被抑制。凋亡蛋白水平下调。FTY720 通过激活 PI3K/AKT/eNOS 途径促进 NO 生成。FTY720 治疗可改善 SAH 大鼠的 CVS 和神经功能缺损。与仅假手术动物相比，非手术组的 FTY720 治疗并未增加死亡率。这些结果表明，FTY720 可通过其抗炎、抗凋亡作用以及促进 NO 生成来缓解 CVS。FTY720 可能对 SAH 患者的临床治疗有效。
