Circulating extracellular vesicles activate the pyroptosis pathway in the brain following ventilation-induced lung injury.

Autor: Chavez L; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Meguro J; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Chen S; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., de Paiva VN; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Zambrano R; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Eterno JM; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Kumar R; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Duncan MR; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Benny M; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Young KC; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Dietrich WD; The Miami Project To Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA., Brambilla R; The Miami Project To Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA., Wu S; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA., Schmidt AF; Department of Pediatrics, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA. aschmidt@med.miami.edu.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2021 Dec 29; Vol. 18 (1), pp. 310. Date of Electronic Publication: 2021 Dec 29.
DOI: 10.1186/s12974-021-02364-z
Abstrakt: Background: Mechanical ventilation of preterm newborns causes lung injury and is associated with poor neurodevelopmental outcomes. However, the mechanistic links between ventilation-induced lung injury (VILI) and brain injury is not well defined. Since circulating extracellular vesicles (EVs) are known to link distant organs by transferring their cargos, we hypothesized that EVs mediate inflammatory brain injury associated with VILI.
Methods: Neonatal rats were mechanically ventilated with low (10 mL/kg) or high (25 mL/kg) tidal volume for 1 h on post-natal day 7 followed by recovery for 2 weeks. Exosomes were isolated from the plasma of these rats and adoptively transferred into normal newborn rats. We assessed the effect of mechanical ventilation or exosome transfer on brain inflammation and activation of the pyroptosis pathway by western blot and histology.
Results: Injurious mechanical ventilation induced similar markers of inflammation and pyroptosis, such as increased IL-1β and activated caspase-1/gasdermin D (GSDMD) in both lung and brain, in addition to inducing microglial activation and cell death in the brain. Isolated EVs were enriched for the exosomal markers CD9 and CD81, suggesting enrichment for exosomes. EVs isolated from neonatal rats with VILI had increased caspase-1 but not GSDMD. Adoptive transfer of these EVs led to neuroinflammation with microglial activation and activation of caspase-1 and GSDMD in the brain similar to that observed in neonatal rats that were mechanically ventilated.
Conclusions: These findings suggest that circulating EVs can contribute to the brain injury and poor neurodevelopmental outcomes in preterm infants with VILI through activation of GSDMD.
(© 2021. The Author(s).)
Databáze: MEDLINE
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