title: Ex vivo (1)H nuclear magnetic resonance spectroscopy reveals systematic alterations in cerebral metabolites as the key pathogenetic mechanism of bilirubin encephalopathy.
abstract: BACKGROUND
  Bilirubin encephalopathy (BE) is a severe neurologic sequelae induced by hyperbilirubinemia in newborns. However, the pathogenetic mechanisms underlying the clinical syndromes of BE remain ambiguous. Ex vivo (1)H nuclear magnetic resonance (NMR) spectroscopy was used to measure changes in the concentrations of cerebral metabolites in various brain areas of newborn 9-day-old rats subjected to bilirubin to explore the related mechanisms of BE.
  
  
  RESULTS
  When measured 0.5 hr after injection of bilirubin, levels of the amino acid neurotransmitters glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) in hippocampus and occipital cortex significantly decreased, by contrast, levels of aspartate (Asp) considerably increased. In the cerebellum, Glu and Gln levels significantly decreased, while GABA, and Asp levels showed no significant differences. In BE 24 hr rats, all of the metabolic changes observed returned to normal in the hippocampus and occipital cortex; however, levels of Glu, Gln, GABA, and glycine significantly increased in the cerebellum.
  
  
  CONCLUSIONS
  These metabolic changes for the neurotransmitters are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons, in a region-specific manner. Changes in energy metabolism and the tricarboxylic acid cycle may also be involved in the pathogenesis of BE.
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. huwenyi933@163.com.|Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. huwenyi933@163.com.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Hu
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. xiaojiechen9@yeah.net.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. yexinjian515@163.com.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Ye
authors.affiliation: Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. zhao_liangcai@126.com.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. huangyanan12@yeah.net.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. zhuhuanle518@126.com.
authors.forename: Huanle
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. yanzhihan_123@163.com.
authors.forename: Zhihan
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. 349201079@qq.com.
authors.forename: Xuebao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. 179928192@qq.com.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. bghu79@126.com.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Bai
authors.affiliation: Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. gaohc27@wmu.edu.cn.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000097:blood; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016002:Discriminant Analysis; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007647:Kernicterus / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D016018:Least-Squares Analysis; D055442:Metabolome; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D014020:Tissue Extracts
chemical_list: D014020:Tissue Extracts; D001663:Bilirubin