Apelin-13 Ameliorates Sepsis-induced Brain Injury by Activating Phosphatase and Tensin Homolog-induced Putative Kinase 1/Parkin-mediated Mitophagy and Modulating Nucleotide-binding Oligomerization Domain-like Receptor Pyrin Domain-Containing 3-driven Pyroptosis in Rats

Journal of physiological investigation., Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Abstract Sepsis is a life-threatening condition that often results in severe brain injury, primarily due to excessive inflammation and mitochondrial dysfunction. This study aims investigate the neuroprotective effects of Apelin-13, bioactive peptide, rat model sepsis-induced injury (SBI). Specifically, we examined role Apelin-13 regulating mitophagy through phosphatase tensin homolog-induced putative kinase 1 (PINK1)/Parkin pathway its impact on nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis oxidative stress. A sepsis was induced male Sprague–Dawley rats ( n = 110, 200–230 g, 12 weeks old) cecal ligation puncture (CLP). The septic received (20 μg/kg, intravenously), either alone or combined with division inhibitor-1 (Mdv-1), inhibitor, before undergoing CLP surgery. Survival rates were assessed over 72-h period, while cognitive function evaluated using Morris water maze 5 days. Western blotting immunohistochemistry utilized measure expression levels NLRP3, cleaved caspase-1, N-terminal fragment gasdermin D, PINK1, Parkin brains rats. In addition, enzyme-linked immunosorbent assays conducted evaluate markers stress inflammatory responses samples. significantly improved survival mitigated treatment enhanced PINK1/Parkin-mediated suppressed NLRP3 inflammasome activation, leading reduction pyroptosis, inflammation, Inhibition by Mdv-1 reversed protective Our findings suggest provides neuroprotection modulating inhibiting pyroptosis. These highlight potential as therapeutic strategy for SBI.

Language: Английский

Protective Effects of Mdivi‐1 on Cognition Disturbance Following Sepsis in Mice via Alleviating Microglia Activation and Polarization

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

Neuroinflammation is one of the essential pathogeneses cognitive damage suffering from sepsis-associated encephalopathy (SAE). Lots evidences showed microglia presented mitochondrial fragmentation during SAE. This study investigated protective effects and novel mechanisms inhibiting via division inhibitor 1 (Mdivi-1) on in The SAE model was performed by cecal ligation puncture (CLP), Mdivi-1 administrated intraperitoneal injection. Morris water maze to assess function. Mitochondrial morphology observed electron microscope or MitoTracker staining. qRT-PCR, immunofluorescence staining, western blots were used detect inflammatory factors protein content, respectively. Flow cytometry polarization hippocampal microglia. Bioinformatics analysis verify hypotheses. administration alleviated sepsis-induced fragmentation, activation, polarization, damage. neuroinflammation oxidative stress suppressed NF-κB Keap1/Nrf2/HO-1 pathways following administration; meanwhile, pyroptosis reduced, which associated with enhanced autophagosome formation p62 elevation administration. Inhibition beneficial disturbance, are related alleviating neuroinflammation, stress, pyroptosis.

Language: Английский

Investigating the role of aspirin on the mortality risk of sepsis-associated encephalopathy: a retrospective study

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Background Sepsis-associated encephalopathy (SAE) is one of the most common complications sepsis. Aspirin can serve as a promising therapeutic candidate and help improve patient outcomes in sepsis its complications. However, efficacy safety aspirin on SAE remains largely unexplored. Methods Patients for this retrospective study were collected from MIMIC-IV (version 3.0). Propensity score matching (PSM) was used to balance baseline characteristics between no group group. The association therapy mortality risk in-hospital, 30-day, 60-day, 90-day, 180-day analyzed by Cox proportional hazards model Kaplan–Meier method. E -value analysis evaluate potential influence unmeasured or unknown confounding factors. Subgroup applied explore differences effects clinical across these various groups. Results Our recruited 4,707 patients total, 2,518 enrolled after PSM. rate consistently significant lower than that curves revealed received exhibited notably higher survival compared those who did not. gastrointestinal hemorrhage had difference two Additionally, pre-ICU group, in-ICU decreased significantly high-dose experienced low-dose Conclusion could reduce 180-day, without increasing hemorrhage. benefits observed persisted regardless exposure timing.

Language: Английский