Intranasal Administration of Extracellular Vesicles Mitigates Apoptosis in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury

Abby Lawson, William Snyder, Eric S. Peeples

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction: Neonatal hypoxic-ischemic brain injury (HIBI) results in significant morbidity and mortality despite current available therapies. Seeking a potential supplemental therapy for HIBI, we investigated the neuroprotective effects of extracellular vesicles derived from neural stem cells (NSC-EVs) and hypoxia-preconditioned brain cells (brain-EVs). Methods: HIBI was induced in postnatal day 9 mice by carotid ligation followed by hypoxia. Following injury, NSC-EVs, brain-EVs, or saline were administered intranasally. Brains were assessed for infarct size, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and caspase-3 expression. Additionally, brain-EV microRNA (miRNA) contents were analyzed by miRNA sequencing. Results: Both EV treated groups showed decreased infarct size (brain-EVs p = 0.004 and NSC-EVs p = 0.052), and although NSC-EV administration resulted in significantly fewer TUNEL+ cells (p = 0.0098), there was no change in caspase-3 expression after NSC-EV administration, suggesting a caspase-3-independent mechanism. Brain-EVs resulted in a nonsignificant decrease in TUNEL+ cells (p = 0.167) but significant decreases in caspase expression (cleaved p = 0.015 and intact p = 0.026). Brain-EVs consistently expressed several miRNAs, including two which have been shown to be downregulated after HIBI: miR-342-3p and miR-330-3p. Conclusion: Understanding the regenerative effects and contents of NSC-EVs and brain-EVs could allow for the development of targeted EV-based therapies that could reduce morbidity and mortality for neonates affected by HIBI.

Original languageEnglish (US)
JournalNeonatology
DOIs
StateAccepted/In press - 2022

Keywords

  • Asphyxia
  • Encephalopathy
  • Exosomes
  • MicroRNA
  • Preconditioning

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Biology

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