Fluoxetine is Neuroprotective in Early Brain Injury via its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model
Hui-Min Hu1• Bin Li2• Xiao-Dong Wang1• Yun-Shan Guo1• Hua Hui1• Hai-Ping Zhang1• Biao Wang1• Da-Geng Huang1• Ding-Jun Hao1,*
1Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710054, China
2Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Northwest University, Xi’an 710054, China
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.
Subarachnoid hemorrhage; Fluoxetine; Blood-brain barrier; Microglial activation; Neuronal apoptosis