Oxygen exposure in early life activates NLRP3 inflammasome in mouse brain

CİLAKER MIÇILI S., Engur D., GENÇ Ş., Ercan I., Soy S., Baysal B., ...More

NEUROSCIENCE LETTERS, vol.738, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 738
  • Publication Date: 2020
  • Doi Number: 10.1016/j.neulet.2020.135389
  • Journal Name: NEUROSCIENCE LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Animal Behavior Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: NLRP3 inflammasome, Hyperoxia, Neuronal damage, White matter damage, Mice, Newborn, HYPEROXIA, NEWBORN, THERAPY, HYPOXIA, TERM
  • Dokuz Eylül University Affiliated: Yes

Abstract

Despite widely known detrimental effects on the developing brain, supplemental oxygen is still irreplaceable in the management of newborn infants with respiratory distress. Identifying downstream mechanisms underlying oxygen toxicity is a key step for development of new neuroprotective strategies. Main purpose of this study is to investigate whether NLRP3 inflammasome activation has a role in the pathogenesis of hyperoxia-induced preterm brain injury. C57BL6 pups were randomly divided into either a hyperoxia group (exposed to 90 % oxygen from birth until postnatal day 7) or control group (maintained in room air; 21 % O-2). At postnatal day 7, all animals were sacrificed. Immunohistochemical examination revealed that hyperoxic exposure for seven days resulted in a global increase in NLRP3 and IL-1 beta immunopositive cells in neonatal mouse brain (p = 0.001). There was a significant rise in Caspase-1 positive cell count in prefrontal and parietal area in the hyperoxia group when compared with controls (p = 0.001). Western blot analysis of brain tissues showed elevated NLRP3, IL-1 beta and Caspase-1 protein levels in the hyperoxia group when compared with controls (p = 0.001). To the best of our knowledge, this is the first study that investigates an association between hyperoxia and establishment of NLRP3 inflammasome in preterm brain.