Fluoxetine is Neuroprotective in Early Brain Injury via its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model
Fluoxetine is Neuroprotective in Early Brain Injury via its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model
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氟西汀通过其在大鼠实验性蛛网膜下腔出血模型中的抗炎和抗凋亡作用，对早期脑损伤具有神经保护作用
DOI：
10.1007/s12264-018-0232-8
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发表时间：
2018-12-01
影响因子：
5.6
通讯作者：
Hao, Ding-Jun
中科院分区：
文献类型：
--
作者：
Hu, Hui-Min;Li, Bin;Hao, Ding-Jun
氟西汀是一种抗抑郁药物，最近被证明在中枢神经系统损伤中具有神经保护作用，但其在蛛网膜下腔出血(SAH)中的作用尚不清楚。在本研究中，我们旨在评价氟西汀是否能减轻SAH后早期脑损伤(EBI)。结果表明，腹腔注射氟西汀(每天10 mg/kg)可显著减轻实验性蛛网膜下腔出血后脑水肿和血脑屏障的破坏、小胶质细胞的激活和神经元的凋亡，表现为减少脑含水量和伊文思蓝渗出，阻止紧密连接蛋白闭锁带-1、克拉丁-5和闭锁蛋白的破坏，减少IBA-1、ED-1和TUNEL染色阳性的细胞，降低IL-1β、IL-6、肿瘤坏死因子-α、丙二醛、3-硝基酪氨酸和8-羟色胺的水平。此外，氟西汀显著改善SAH后EBI的神经功能障碍和长期感觉运动行为缺陷。提示氟西汀对实验性蛛网膜下腔出血有神经保护作用。
Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.