Acute and chronic immunomodulatory changes in rat liver after fetal and perinatal asphyxia

E. Vlassaks, M. Nikiforou, E. Strackx, M. Hutten, O. Bekers, D. Gazzolo, G. Li Volti, P. Martinez-Martinez, B.W. Kramer, A.W. Gavilanes

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Hypoxic-ischemic encephalopathy (HIE) caused by fetal and perinatal asphyxia is an important cause of mortality in the neonatal period. Not only will asphyxia affect the brain but also other organs such as the liver and kidneys. Interestingly, it has been shown that liver damage is proportional to the severity of the asphyctic insult, implying an association between liver impairment and HIE. Accordingly, we investigated in an established rat model the acute and chronic hepatic response to both fetal (FA) and perinatal asphyxia (PA). In addition, we assessed whether fetal asphyctic preconditioning (PC) would have any beneficial effect on the liver. Inflammation, ceramide signaling and hepatocellular damage were analyzed in the livers of newborn and adult rats at several short- and long-term time points after both FA and PA. We found that although FA induced an acute inflammatory response, apoptotic mRNA levels and oxidative DNA damage were decreased at 96 h post FA. Whereas increased IL-6 and IL-10 mRNA levels were observed after PA, the combination of FA and PA (PC) attenuated the inflammatory response. Moreover, 6 h after PA anti-apoptotic genes were downregulated and associated with less lipid peroxidation, while preconditioned animals were comparable to controls. In summary, asphyctic PC seems to have an acute protective effect on the liver by modulating the inflammatory, apoptotic and anti-oxidative response. More insight into the hepatic response to asphyxia is necessary, as disturbed hepatic function is associated with metabolic diseases in later life.
Original languageEnglish
Pages (from-to)98-108
Number of pages11
JournalJournal of developmental origins of health and disease
Volume5
Issue number2
DOIs
Publication statusPublished - Apr 2014

Keywords

  • asphyxia
  • inflammation
  • liver
  • preconditioning
  • rat
  • HYPOXIC-ISCHEMIC ENCEPHALOPATHY
  • NECROSIS-FACTOR-ALPHA
  • LIPID-METABOLISM
  • CEREBROSPINAL-FLUID
  • REPERFUSION INJURY
  • BIRTH ASPHYXIA
  • TNF-ALPHA
  • BRAIN
  • INTERLEUKIN-6
  • APOPTOSIS

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