Department of Clinical Pharmacy, Luoyang Central Hospital Affiliated to Zhengzhou University, #288 Zhongzhou Middle Road, Xigong District, Luoyang, 471009, Henan Province, China.
Neurotox Res. 2020 Oct;38(3):733-740. doi: 10.1007/s12640-020-00246-5. Epub 2020 Jul 1.
Stroke is one of the leading causes of mortality in cardiovascular diseases. The disruption of the brain-blood barrier is the common feature of stroke-related complications. Safinamide is a newly approved add-on drug to treat Parkinson's disease, and previously studies suggest safinamide could have a potential role on neuroprotection. In this study, we investigated its preventive effect in both acutely induced stroke animals and brain endothelial cells. By the induction of middle cerebral artery occlusion (MCAO) in mice, we established a transit stroke model. Mice were administered 90 mg/kg/day safinamide prior to MCAO and during ischemia and reperfusion. Results indicate that the administration of safinamide significantly ameliorated MCAO-caused cerebral infarction volume, neurological deficit, disruption of the brain-blood barrier (BBB), and impaired expression of tight junction protein occludin and ZO-1. In cultured brain endothelial cell line bEND.3, pre-treatment with safinamide alleviated oxygen and glucose deprivation/reperfusion (OGD/R) caused cytotoxicity and favored cell survival. Transwell assay showed safinamide prevented OGD/R-induced hyperpermeability and the reduction of occludin and ZO-1. Moreover, safinamide treatment suppressed OGD/R-caused induction of metalloproteinase 2 (MMP-2) and 9 (MMP-9). Collectively, our data conclude safinamide has a preventive neuroprotection in acute stroke animals. The protective effect of safinamide on brain endothelial cells suggests the drug may ameliorate BBB disruption and improve vascular integrity in ischemia stroke.
中风是心血管疾病导致死亡的主要原因之一。血脑屏障的破坏是中风相关并发症的共同特征。沙芬酰胺是一种新批准的治疗帕金森病的附加药物，先前的研究表明沙芬酰胺可能具有神经保护作用。在这项研究中，我们研究了它在急性诱导中风动物和脑内皮细胞中的预防作用。通过诱导小鼠大脑中动脉闭塞（MCAO），我们建立了一个短暂性中风模型。在 MCAO 之前和缺血再灌注期间，给予小鼠 90mg/kg/天的沙芬酰胺。结果表明，沙芬酰胺的给药显著改善了 MCAO 引起的脑梗死体积、神经功能缺损、血脑屏障（BBB）的破坏以及紧密连接蛋白 occludin 和 ZO-1 的表达受损。在体外培养的脑内皮细胞系 bEND.3 中，沙芬酰胺预处理减轻了氧和葡萄糖剥夺/再灌注（OGD/R）引起的细胞毒性并促进了细胞存活。Transwell 测定显示沙芬酰胺可防止 OGD/R 诱导的通透性增加以及 occludin 和 ZO-1 的减少。此外，沙芬酰胺处理抑制了 OGD/R 引起的基质金属蛋白酶 2（MMP-2）和 9（MMP-9）的诱导。综上所述，我们的数据表明沙芬酰胺在急性中风动物中具有预防神经保护作用。沙芬酰胺对脑内皮细胞的保护作用表明，该药物可能改善缺血性中风中的血脑屏障破坏和血管完整性。
