CARD8 and IL1B Polymorphisms Influence MRI Brain Patterns in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia.

Katarina Esih,Katja Goričar,Vita Dolžan,Aneta Soltirovska-Šalamon,Zvonka Rener-Primec

doi:10.3390/antiox10010096

Katarina Esih, Katja Goričar + Show 3 more

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https://doi.org/10.3390/antiox10010096

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Abstract

Inflammation and oxidative stress are recognized as important contributors of brain injury in newborns due to a perinatal hypoxic-ischemic (HI) insult. Genetic variability in these pathways could influence the response to HI and the outcome of brain injury. The aim of our study was to evaluate the impact of common single-nucleotide polymorphisms in the genes involved in inflammation and response to oxidative stress on brain injury in newborns after perinatal HI insult based on the severity and pattern of magnetic resonance imaging (MRI) findings. The DNA of 44 subjects was isolated from buccal swabs. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1B rs16944, IL1B rs1143623, IL1B rs1071676, TNF rs1800629, CAT rs1001179, SOD2 rs4880, and GPX1 rs1050450. Polymorphism in CARD8 was found to be protective against HI brain injury detected by MRI overall findings. Polymorphisms in IL1B were associated with posterior limb of internal capsule, basal ganglia, and white matter brain patterns determined by MRI. Our results suggest a possible association between genetic variability in inflammation- and antioxidant-related pathways and the severity of brain injury after HI insult in newborns.

Highlights

Perinatal hypoxic-ischemic encephalopathy (HIE) results from compromised blood flow and/or oxygen delivery to the newborn baby’s brain and is one of the leading causes of long-term neurological disability in children [1]
CARD8 rs2043211 was associated with lower overall rates of brain injury and lower brainstem and cortex damage after HIE in newborns treated with HT
Our study demonstrated the association of some polymorphisms in the antioxidant and inflammatory pathways and magnetic resonance imaging (MRI) abnormalities in newborns after HI insult

Summary

Introduction

Perinatal hypoxic-ischemic encephalopathy (HIE) results from compromised blood flow and/or oxygen delivery to the newborn baby’s brain and is one of the leading causes of long-term neurological disability in children [1]. The only established therapy for HIE, therapeutic hypothermia (HT), implemented in 2010, improves survival and lowers long-term disability rates, but it is only partially effective [4]. Two methods of cooling have been used in clinical trials—. Whole-body cooling is recommended preferentially because it is easier to set up and use, less expensive, provides better access to EEGs, and is more readily available. Studies suggest that hypothermia exerts a neuroprotective effect by altering several different molecular pathways and affects metabolism, brain perfusion, the release of excitatory amino acids, apoptosis, and antioxi-

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