ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2023
Fluoxetine alleviates postoperative cognitive dysfunction by attenuating TLR4/MyD88/NF-κB signaling pathway activation in aged mice.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Exercise and fluoxetine in Alzheimer's disease: Molecular mechanisms of synergistic and antagonistic effects (Review).International journal of molecular medicine · 2026Review
- Berberine Alleviates Lipopolysaccharide-Induced Impairments in Neuroplasticity and Spatial Memory by Modulating Microglial Polarization via MAPK Signaling Inhibition.Neural plasticity · 2026Article
- Investigating the therapeutic mechanism of Puerarin in vascular dementia: an integrated approach combining network pharmacology and experimental validation.Frontiers in pharmacology · 2026Article
- Neuroinflammation in postoperative cognitive dysfunction: the multi-target potential of esketamine in modulating microglial responses and synaptic integrity.Frontiers in molecular neuroscience · 2026Review
- Ononin, a Natural Isoflavone Glycoside, Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Regulating Neuroinflammation and Oxidative Stress.Brain and behavior · 2025Article
- Review
- MyD88 and Its Inhibitors in Cancer: Prospects and Challenges.Biomolecules · 2024Review
- Surgery induces neurocognitive disorder via neuroinflammation and glymphatic dysfunction in middle-aged mice with brain lymphatic drainage impairment.Frontiers in neuroscience · 2024Article
- mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice.International journal of biological sciences · 2024Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
OBJECTIVE AND
designPostoperative cognitive dysfunction (POCD) is a common complication following surgery among elderly patients. Emerging evidence demonstrates that neuroinflammation plays a pivotal role in the pathogenesis of POCD. This study tested the hypothesis that fluoxetine can protect against POCD by suppressing hippocampal neuroinflammation through attenuating TLR4/MyD88/NF-κB signaling pathway activation. SUBJECTS: Aged C57BL/6 J male mice (18 months old) were studied. TREATMENT: Aged mice were intraperitoneally injected with fluoxetine (10 mg/kg) or saline for seven days before splenectomy. In addition, aged mice received an intracerebroventricular injection of a TLR4 agonist or saline seven days before splenectomy in the rescue experiment.
methodsOn postoperative days 1, 3, and 7, we assessed hippocampus-dependent memory, microglial activation status, proinflammatory cytokine levels, protein levels related to the TLR4/MyD88/NF-κB signaling pathway, and hippocampal neural apoptosis in our aged mouse model.
resultsSplenectomy induced a decline in spatial cognition, paralleled by parameters indicating exacerbation of hippocampal neuroinflammation. Fluoxetine pretreatment partially restored the deteriorated cognitive function, downregulated proinflammatory cytokine levels, restrained microglial activation, alleviated neural apoptosis, and suppressed the increase in TLR4, MyD88, and p-NF-κB p65 in microglia. Intracerebroventricular injection of LPS (1 μg, 0.5 μg/μL) before surgery weakened the effect of fluoxetine.
conclusionFluoxetine pretreatment suppressed hippocampal neuroinflammation and mitigated POCD by inhibiting microglial TLR4/MyD88/NF-κB pathway activation in aged mice.
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