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

Published online by Cambridge University Press:  22 January 2014

E. Vlassaks ,
M. Nikiforou ,
E. Strackx ,
M. Hütten ,
O. Bekers ,
D. Gazzolo ,
G. Li Volti ,
P. Martinez-Martinez ,
B. W. Kramer  and
A. W. D. Gavilanes
E. Vlassaks
Affiliation:
Department of Neuropsychology, Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands Department of Pediatrics, Division of Neonatology, Maastricht University Medical Center, Maastricht, the Netherlands School for Oncology and Developmental Biology Maastricht (GROW), Maastricht University, Maastricht, the Netherlands
M. Nikiforou
Affiliation:
Department of Neuropsychology, Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands Department of Pediatrics, Division of Neonatology, Maastricht University Medical Center, Maastricht, the Netherlands
E. Strackx
Affiliation:
Department of Neuropsychology, Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands Department of Pediatrics, Division of Neonatology, Maastricht University Medical Center, Maastricht, the Netherlands
M. Hütten
Affiliation:
Department of Pediatrics, Division of Neonatology, Maastricht University Medical Center, Maastricht, the Netherlands Department of Childhood and Adolescent Medicine, Division of Neonatology, Medical Faculty RWTH Aaachen, University Hospital, Germany
O. Bekers
Affiliation:
Department of Clinical Chemistry, Maastricht University Medical Center, Maastricht, the Netherlands
D. Gazzolo
Affiliation:
Department of Pediatrics, Obstetrics and Reproductive Medicine, Siena, Italy
G. Li Volti
Affiliation:
Department of Drug Sciences, University of Catania, Catania, Italy
P. Martinez-Martinez
Affiliation:
Department of Neuropsychology, Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands
B. W. Kramer
Affiliation:
Department of Neuropsychology, Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands Department of Pediatrics, Division of Neonatology, Maastricht University Medical Center, Maastricht, the Netherlands School for Oncology and Developmental Biology Maastricht (GROW), Maastricht University, Maastricht, the Netherlands
A. W. D. Gavilanes*
Affiliation:
Department of Neuropsychology, Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands Department of Pediatrics, Division of Neonatology, Maastricht University Medical Center, Maastricht, the Netherlands
*
*Address for correspondence: A. W. D. Gavilanes, MD, PhD, Associate Professor, Department of Pediatrics, Division of Neonatology, Maastricht University Medical Centre, Postbus 5800, 6202AZ Maastricht, the Netherlands. (Email danilo.gavilanes@mumc.nl)
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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.

Keywords

asphyxiainflammationliverpreconditioningrat
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 5 , Issue 2 , April 2014 , pp. 98 - 108
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

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Footnotes

†

Equal contribution.

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