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Neuropediatrics 2024; 55(01): 023-031
DOI: 10.1055/s-0043-1776286
Original Article

Effects of Neonatal Hypoxic-Ischemic Injury on Brain Sterol Synthesis and Metabolism

Amanda M. Dave
1   Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, United States
2   Department of Pediatrics, Children's Hospital and Medical Center, Omaha, Nebraska, United States
3   Child Health Research Institute, Omaha, Nebraska, United States
,
Ned A. Porter
4   Department of Chemistry, Vanderbilt University, Nashville, Tennessee, United States
,
Zeljka Korade
1   Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, United States
3   Child Health Research Institute, Omaha, Nebraska, United States
5   Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States
,
Eric S. Peeples
1   Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, United States
2   Department of Pediatrics, Children's Hospital and Medical Center, Omaha, Nebraska, United States
3   Child Health Research Institute, Omaha, Nebraska, United States
› Author Affiliations Funding This study is supported by the Child Health Research Institute, University of Nebraska Medical Center.
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Abstract

Background Neonatal hypoxic-ischemic brain injury (HIBI) results from disruptions to blood supply and oxygen in the perinatal brain. The goal of this study was to measure brain sterol metabolites and plasma oxysterols after injury in a neonatal HIBI mouse model to assess for potential therapeutic targets in the brain biochemistry as well as potential circulating diagnostic biomarkers.

Methods Postnatal day 9 CD1-IGS mouse pups were randomized to HIBI induced by carotid artery ligation followed by 30 minutes at 8% oxygen or to sham surgery and normoxia. Brain tissue was collected for sterol analysis by liquid chromatography with tandem mass spectrometry (LC–MS/MS). Plasma was collected for oxysterol analysis by LC–MS/MS.

Results There were minimal changes in brain sterol concentrations in the first 72 hours after HIBI. In severely injured brains, there was a significant increase in desmosterol, 7-DHC, 8-DHC, and cholesterol 24 hours after injury in the ipsilateral tissue. Lanosterol, 24-dehydrolathosterol, and 14-dehydrozymostenol decreased in plasma 24 hours after injury. Severe neonatal HIBI was associated with increased cholesterol and sterol precursors in the cortex at 24 hours after injury.

Conclusions Differences in plasma oxysterols were seen at 24 hours but were not present at 30 minutes after injury, suggesting that these sterol intermediates would be of little value as early diagnostic biomarkers.

Keywords

cholesterol - encephalopathy - LC–MS/MS - metabolomics

Supplementary Material



Publication History

Received: 02 May 2023

Accepted: 18 September 2023

Article published online:
23 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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