Mangiferin alleviated poststroke cognitive impairment by modulating lipid metabolism in cerebral ischemia/reperfusion rats

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 977, P. 176724 - 176724

Published: June 6, 2024

Language: Английский

Rat models of postintracerebral hemorrhage pneumonia induced by nasal inoculation with Klebsiella pneumoniae or intratracheal inoculation with LPS

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 8, 2025

A stable and reproducible experimental bacterial pneumonia model postintracerebral hemorrhage (ICH) is necessary to help investigating the pathogenesis novel treatments of Stroke-associated (SAP). To establish a Gram-negative pneumonia-complicating ICH rat an acute lung injury (ALI)-complicating model. We established two standardized models post-ICH by nasal inoculation with Klebsiella pneumoniae (Kp) or intratracheal lipopolysaccharide (LPS). Survival neurological scores were monitored. Magnetic resonance imaging was performed evaluate hematoma volume. Abdominal aortic blood collected for leukocyte counting, serum isolated determine concentrations S100β proinflammatory cytokines using ELISAs. Histopathological changes brain, gut assessed hematoxylin-eosin staining. Lung immunofluorescence staining myeloperoxidase (MPO). Bronchoalveolar lavage fluid supernatant prepared measure MPO activity. Ileum tight junction proteins ZO-1 γδ TCRs/IL-17A Alcian blue-nuclear fast red acidic mucins. Feces collected, 16S rRNA sequencing, untargeted metabolomics Spearman's correlation analyses explore microbiota, metabolites their interactions. In Kp-induced rats, we demonstrated that Kp challenge caused more severe deficits, brain damage, neuroinflammation, aggravated injury. Disruptions intestinal structure barrier reductions protective IL-17A-producing γδT cells also observed. exacerbated microbiota dysbiosis fecal metabolic profile disorders, which characterized abnormal sphingolipid metabolism especially elevated ceramide levels; increased levels neurotoxic quinolinic acid upregulation tryptophan (Trp)-serotonin-melatonin pathway. further revealed reduction depletion some beneficial bacteria, such as Allobaculum Faecalitalea, blooming opportunistic pathogens, Turicibacter, Dietzia, Corynebacterium Clostridium_sensu_stricto_1 in SAP rats associated disordered Trp metabolism. Using LPS-induced ALI complicating model, SAP-induced histopathology injuries; peripheral immune disorders intense pulmonary inflammatory responses. These may be highly useful screening optimizing potential SAP. Moreover, differential genera identified above seem promising therapeutic targets.

Language: Английский

Comparative Targeted Metabolomics in Ischemic Stroke Patients: Profiling Thrombi and Serums Samples for Identification of Stroke-related Metabolites

Published: Feb. 21, 2024

Ischemic stroke is one of the leading causes death and permanent disability in world. Rapid diagnosis intervention are crucial for reducing its consequences on individuals societies. Identifying reliable biomarkers early detection, prognostics therapy a criti-cal imperative improving patient treatment. Metabolomics has been shown as promising tool biomarker discovery since many post-ischemic metabolites can found plasma or serum patient. In this research, we have performed comparative targeted metabolomic analysis thrombi, serums healthy control order to determine alteration patients’ metabolome. The most statistically altered characterized compared were glutamate serotonin, followed by several lipid (phospholipids triacylglycerols) glucose. thrombi patient’s serums, significantly classified li-pids, with choline-containing phospholipids sphingomyelins having highest discrimi-natory score. results study could help understanding roles different meta-bolic changes occurring during thrombosis cerebral ischemia possibly suggest new metabolic ischemic stroke.

Language: Английский