Study summary · research use only
Sepsis Encephalopathy Is Partly Mediated by miR370-3p-Induced Mitochondrial Injury but Attenuated by BAM15 in Cecal Ligation and Puncture Sepsis Male Mice
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this male mouse study, BAM15, a mitochondrial uncoupling agent, was tested in a cecal ligation and puncture (CLP) sepsis model alongside in vitro experiments. The abstract reports BAM15 was associated with improved survival, reduced organ histology damage in kidneys and livers, decreased spleen apoptosis, reduced brain injury markers (SHIRPA score, serum s100β, brain miR370-3p, brain TNF-α), reduced systemic inflammation, and reduced blood-brain barrier damage. Brain miR arrays showed miR370-3p elevation at 24 h but not 120 h post-CLP. LPS or TNF-α increased miR370-3p in PC12 neuron cells, and sepsis factors damaged mitochondria and reduced cell ATP, changes attenuated by BAM15, which was also associated with reduced mitochondrial injury and pro-inflammatory markers in bone-marrow-derived macrophages.
Abstract
BAM15 (a mitochondrial uncoupling agent) was tested on cecal ligation and puncture (CLP) sepsis mice with in vitro experiments. BAM15 attenuated sepsis as indicated by survival, organ histology (kidneys and livers), spleen apoptosis (activated caspase 3), brain injury (SHIRPA score, serum s100β, serum miR370-3p, brain miR370-3p, brain TNF-α, and apoptosis), systemic inflammation (cytokines, cell-free DNA, endotoxemia, and bacteremia), and blood-brain barrier (BBB) damage (Evan's blue dye and the presence of green fluorescent E. coli in brain after an oral administration). In parallel, brain miR arrays demonstrated miR370-3p at 24 h but not 120 h post-CLP, which was correlated with metabolic pathways. Either lipopolysaccharide (LPS) or TNF-α upregulated miR370-3p in PC12 (neuron cells). An activation by sepsis factors (LPS, TNF-α, or miR370-3p transfection) damaged mitochondria (fluorescent color staining) and reduced cell ATP, possibly through profound mitochondrial activity (extracellular flux analysis) that was attenuated by BAM15. In bone-marrow-derived macrophages, LPS caused mitochondrial injury, decreased cell ATP, enhanced glycolysis activity (extracellular flux analysis), and induced pro-inflammatory macrophages (iNOS and IL-1β) which were neutralized by BAM15. In conclusion, BAM15 attenuated sepsis through decreased mitochondrial damage, reduced neuronal miR370-3p upregulation, and induced anti-inflammatory macrophages. BAM15 is proposed to be used as an adjuvant therapy against sepsis hyperinflammation.
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