Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, 11795, Egypt.
J Neuroimmune Pharmacol. 2023 Dec;18(4):657-673. doi: 10.1007/s11481-023-10093-8. Epub 2023 Nov 13.
Cerebral ischemia reperfusion (I/R) is one of the neurovascular diseases which leads to severe brain deterioration. Haemorrhagic transformation (HT) is the main complication of ischemic stroke. It exacerbates by reperfusion, causing a more deleterious effect on the brain and death. The current study explored the protective effect of sertraline (Sert) against cerebral I/R in rats by inhibiting HT, together with the molecular pathways involved in this effect. Forty-eight wister male rats were divided into 4 groups: Sham, Sert + Sham, I/R, and Sert + I/R. The ischemic model was induced by bilateral occlusion of the common carotid artery for 20 min, then reperfusion for 24 h. Sertraline (20 mg/kg, p.o.) was administrated for 14 days before exposure to ischemia. Pre-treatment with Sert led to a significant attenuation of oxidative stress and inflammation. In addition, Sert attenuated phosphorylation of extracellular regulated kinases and nuclear factor kappa-p65 expression, consequently modulating microglial polarisation to M2 phenotype. Moreover, Sert prevented the hemorrhagic transformation of ischemic stroke as indicated by the notable decrease in neuronal expression of CD163, activity of Heme oxygenase-2 and matrix metalloproteinase-2 and 9 levels. In the same context, Sert decreased levels of autophagy and apoptotic markers. Furthermore, histological examination, Toluidine blue, and Prussian blue stain aligned with the results. In conclusion, Sert protected against cerebral I/R damage by attenuating oxidative stress, inflammation, autophagy, and apoptotic process. It is worth mentioning that our study was the first to show that Sert inhibited hemorrhagic transformation. The protective effect of sertraline against injury induced by cerebral ischemia reperfusion via inhibiting Hemorrhagic transformation.
脑缺血再灌注（I/R）是导致严重脑恶化的神经血管疾病之一。出血转化（HT）是缺血性中风的主要并发症。再灌注使其恶化，对大脑造成更具危害性的影响并导致死亡。本研究通过抑制 HT 来探讨舍曲林（Sert）对大鼠脑 I/R 的保护作用，以及涉及该作用的分子途径。48 只雄性 Wistar 大鼠分为 4 组：假手术（Sham）、Sert+Sham、I/R 和 Sert+I/R。通过双侧颈总动脉闭塞 20 分钟诱导缺血模型，然后再灌注 24 小时。暴露于缺血前 14 天给予 Sert（20 mg/kg，口服）。Sert 的预处理可显著减轻氧化应激和炎症。此外，Sert 减弱了细胞外调节激酶和核因子 kappa-p65 的磷酸化，从而调节小胶质细胞向 M2 表型的极化。此外，Sert 可防止缺血性中风的出血转化，表现为神经元 CD163 表达、血红素加氧酶-2 活性和基质金属蛋白酶-2 和 9 水平的显著降低。同样，Sert 降低了自噬和凋亡标志物的水平。此外，组织学检查、甲苯胺蓝和普鲁士蓝染色与结果一致。总之，Sert 通过减轻氧化应激、炎症、自噬和凋亡过程来保护大脑免受 I/R 损伤。值得一提的是，我们的研究首次表明 Sert 抑制了出血转化。舍曲林通过抑制出血转化对脑缺血再灌注损伤的保护作用。
