Abstract

BackgroundBilirubin 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 vivo1H 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.ResultsWhen 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.ConclusionsThese 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.

Highlights

  • Neonatal hyperbilirubinemia, which is caused by immaturity of hepatic conjugation and clearance processes for unconjugated bilirubin (UCB) [1], is a common and important pathological condition that occurs in approximately 60% of all term newborns and 80% of all pre-term infants [2]

  • nuclear magnetic resonance (NMR) is a powerful approach for studying brain energy metabolism, neurotransmission, and glial–neuronal interactions [16,17], and it has been previously used to investigate the changes in brain metabolism of various encephalopathies [14,15,18]

  • Changes in the concentrations of cerebral metabolites in the hippocampus, occipital cortex, and cerebellum of rats subjected to Bilirubin encephalopathy (BE) 0.5, 4, and 24 hrs by ex vivo 1H NMR spectroscopy were comprehensively reported

Read more

Summary

Introduction

Neonatal hyperbilirubinemia, which is caused by immaturity of hepatic conjugation and clearance processes for unconjugated bilirubin (UCB) [1], is a common and important pathological condition that occurs in approximately 60% of all term newborns and 80% of all pre-term infants [2]. The outcome for the majority of babies is benign, but untreated neonates or newborns with very high UCB levels can develop yellow staining and the neurological dysfunction characterizing bilirubin encephalopathy (BE). Researchers have indicated that UCB induces enhanced oxidative stress, alterations in neurogenesis, neuritogenesis, synaptogenesis, and disruption of neuronal network dynamics [9]. Which of these mechanisms is most important in the causation of the clinical syndromes of BE has yet to be investigated. Ex vivo 1H 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

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call