Fluoxetine is Neuroprotective in Early Brain Injury via its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model
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.
KeywordsSubarachnoid hemorrhage Fluoxetine Blood-brain barrier Microglial activation Neuronal apoptosis
This work was supported by the National Natural Science Foundation of China (81601938), the Natural Science Fund of Shaanxi Province (2016JQ8010), and the Science and Technology Projects Fund of Xi’an city (2016050SF/YX06(6)).
Compliance with Ethical Standards
Conflict of interest
All authors declare that there are no conflicts of interest.
- 8.Marquez-Romero JM, Arauz A, Ruiz-Sandoval JL, Cruz-Estrada Ede L, Huerta-Franco MR, Aguayo-Leytte G, et al. Fluoxetine for motor recovery after acute intracerebral hemorrhage (FMRICH): study protocol for a randomized, double-blind, placebo-controlled, multicenter trial. Trials 2013, 14: 77.CrossRefGoogle Scholar