Acute LPS sensitization and continuous infusion exacerbates hypoxic brain injury in a piglet model of neonatal encephalopathy

Kathryn A Martinello, Christopher Meehan, Adnan Avdic-Belltheus, Ingran Lingam, Sara Ragab, Mariya Hristova, Cally J Tann, Donald Peebles, Henrik Hagberg, Tim G A M Wolfs, Nigel Klein, Ilias Tachtsidis, Xavier Golay, Boris W Kramer, Bobbi Fleiss, Pierre Gressens, Nicola J Robertson

Research output: Contribution to journalArticlepeer-review

Abstract

Co-existing infection/inflammation and birth asphyxia potentiate the risk of developing neonatal encephalopathy (NE) and adverse outcome. In a newborn piglet model we assessed the effect of E. coli lipopolysaccharide (LPS) infusion started 4 h prior to and continued for 48 h after hypoxia on brain cell death and systemic haematological changes compared to LPS and hypoxia alone. LPS sensitized hypoxia resulted in an increase in mortality and in brain cell death (TUNEL positive cells) throughout the whole brain, and in the internal capsule, periventricular white matter and sensorimotor cortex. LPS alone did not increase brain cell death at 48 h, despite evidence of neuroinflammation, including the greatest increases in microglial proliferation, reactive astrocytosis and cleavage of caspase-3. LPS exposure caused splenic hypertrophy and platelet count suppression. The combination of LPS and hypoxia resulted in the highest and most sustained systemic white cell count increase. These findings highlight the significant contribution of acute inflammation sensitization prior to an asphyxial insult on NE illness severity.

Original languageEnglish
Pages (from-to)10184
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 15 Jul 2019

Keywords

  • Animals
  • Animals, Newborn
  • Asphyxia/metabolism
  • Asphyxia Neonatorum/physiopathology
  • Brain/metabolism
  • Brain Diseases/metabolism
  • Brain Injuries/metabolism
  • Cell Death
  • Disease Models, Animal
  • Escherichia coli
  • Hypoxia/metabolism
  • Hypoxia-Ischemia, Brain/metabolism
  • Inflammation/metabolism
  • Lipopolysaccharides/adverse effects
  • Male
  • Swine
  • White Matter/metabolism

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