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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_AF6E83A093E9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neurometabolic changes in a rat pup model of type C hepatic encephalopathy depend on age at liver disease onset.
Journal
Metabolic brain disease
Author(s)
Simicic D., Rackayova V., Braissant O., Toso C., Oldani G., Sessa D., McLin V.A., Cudalbu C.
ISSN
1573-7365 (Electronic)
ISSN-L
0885-7490
Publication state
Published
Issued date
08/2023
Peer-reviewed
Oui
Volume
38
Number
6
Pages
1999-2012
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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 ( <sup>1</sup> H 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 <sup>1</sup> H MRS methodological limitations in field strength of clinical magnet.
Keywords
Humans, Adult, Child, Rats, Animals, Hepatic Encephalopathy/metabolism, Glutamine/metabolism, Magnetic Resonance Spectroscopy, Liver Diseases/metabolism, Brain/metabolism, Lactic Acid/metabolism, 1H MRS, Bile duct ligation, Chronic liver disease, Neurodevelopment, Type C hepatic encephalopathy
Pubmed
Web of science
Open Access
Yes
Create date
15/05/2023 14:42
Last modification date
04/10/2023 7:14
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