Fluoxetine attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage: a possible role for the regulation of TLR4/MyD88/NF-κB signaling pathway

Autor: Jingsen Chen, Lin Wang, Gao Chen, Guo-ping Guan, Cong Qian, Chun Wang, Wu Ruan, Jianru Li, Jing Cai, Hai-zhou Pan, Fuyi Liu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Brain Edema
Pharmacology
lcsh:RC346-429
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Neuroinflammation
Granulocyte Colony-Stimulating Factor
Evans Blue
Sulfonamides
Microglia
General Neuroscience
Microfilament Proteins
NF-kappa B
Extravasation
Neuroprotective Agents
medicine.anatomical_structure
Neurology
Blood-Brain Barrier
Cytokines
Signal Transduction
medicine.drug
Early brain injury
Subarachnoid hemorrhage
Recombinant Fusion Proteins
Immunology
Neuroprotection
03 medical and health sciences
Cellular and Molecular Neuroscience
Fluoxetine
medicine
Animals
cardiovascular diseases
lcsh:Neurology. Diseases of the nervous system
business.industry
Research
Calcium-Binding Proteins
medicine.disease
Rats
nervous system diseases
Toll-Like Receptor 4
Disease Models
Animal
030104 developmental biology
Gene Expression Regulation
chemistry
Brain Injuries
Myeloid Differentiation Factor 88
TLR4
Interleukin-3
business
030217 neurology & neurosurgery
Zdroj: Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-14 (2018)
Journal of Neuroinflammation
ISSN: 1742-2094
Popis: Background Neuroinflammation is closely associated with functional outcome in subarachnoid hemorrhage (SAH) patients. Our recent study demonstrated that fluoxetine inhibited NLRP3 inflammasome activation and attenuated necrotic cell death in early brain injury after SAH, while the effects and potential mechanisms of fluoxetine on neuroinflammation after SAH have not been well-studied yet. Methods One hundred and fifty-three male SD rats were subjected to the endovascular perforation model of SAH. Fluoxetine (10 mg/kg) was administered intravenously at 6 h after SAH induction. TAK-242 (1.5 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h after SAH. SAH grade, neurological scores, brain water content, Evans blue extravasation, immunofluorescence/TUNEL staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were performed. Results Fluoxetine administration attenuated BBB disruption, brain edema, and improved neurological function after SAH. In addition, fluoxetine alleviated the number of Iba-1-positive microglia/macrophages, neutrophil infiltration, and cell death. Moreover, fluoxetine reduced the levels of pro-inflammatory cytokines, downregulated the expression of TLR4 and MyD88, and promoted the nuclear translocation of NF-κB p65, which were also found in rats with TAK-242 administration. Combined administration of fluoxetine and TAK-242 did not enhance the neuroprotective effects of fluoxetine. Conclusion Fluoxetine attenuated neuroinflammation and improved neurological function in SAH rats. The potential mechanisms involved, at least in part, TLR4/MyD88/NF-κB signaling pathway. Electronic supplementary material The online version of this article (10.1186/s12974-018-1388-x) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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