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  4. Neurometabolic changes in a rat pup model of type C hepatic encephalopathy depend on age at liver disease onset
 
research article

Neurometabolic changes in a rat pup model of type C hepatic encephalopathy depend on age at liver disease onset

Simicic, Dunja  
•
Rackayova, Veronika  
•
Braissant, Olivier
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May 6, 2023
Metabolic Brain Disease

Chronic liver disease (CLD) is a serious condition where various toxins present in the blood affect the brain leading to type C hepatic encephalopathy (HE). Both adults and children are impacted, while children may display unique vulnerabilities depending on the affected window of brain development.We aimed to use the advantages of high field proton Magnetic Resonance Spectroscopy (H-1 MRS) to study longitudinally the neurometabolic and behavioural effects of Bile Duct Ligation (animal model of CLD-induced type C HE) on rats at post-natal day 15 (p15) to get closer to neonatal onset liver disease. Furthermore, we compared two sets of animals (p15 and p21-previously published) to evaluate whether the brain responds differently to CLD according to age onset.We showed for the first time that when CLD was acquired at p15, the rats presented the typical signs of CLD, i.e. rise in plasma bilirubin and ammonium, and developed the characteristic brain metabolic changes associated with type C HE (e.g. glutamine increase and osmolytes decrease). When compared to rats that acquired CLD at p21, p15 rats did not show any significant difference in plasma biochemistry, but displayed a delayed increase in brain glutamine and decrease in total-choline. The changes in neurotransmitters were milder than in p21 rats. Moreover, p15 rats showed an earlier increase in brain lactate and a different antioxidant response. These findings offer tentative pointers as to which neurodevelopmental processes may be impacted and raise the question of whether similar changes might exist in humans but are missed owing to H-1 MRS methodological limitations in field strength of clinical magnet.

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Type
research article
DOI
10.1007/s11011-023-01210-w
Web of Science ID

WOS:000982880700001

Author(s)
Simicic, Dunja  
Rackayova, Veronika  
Braissant, Olivier
Toso, Christian
Oldani, Graziano
Sessa, Dario
McLin, Valerie A.
Cudalbu, Cristina  
Date Issued

2023-05-06

Publisher

SPRINGER/PLENUM PUBLISHERS

Published in
Metabolic Brain Disease
Subjects

Endocrinology & Metabolism

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Neurosciences

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Endocrinology & Metabolism

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Neurosciences & Neurology

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chronic liver disease

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type c hepatic encephalopathy

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neurodevelopment

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bile duct ligation

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h-1 mrs

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proton mr spectroscopy

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brain-cells

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children

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glutathione

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astrocytes

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ascorbate

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vulnerability

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dysfunction

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myelination

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myoinositol

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
CIBM  
Available on Infoscience
June 5, 2023
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/198068
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