Longitudinal neurometabolic changes in the hippocampus of a rat model of chronic hepatic encephalopathy

Braissant, Olivier; Račkayová, Veronika; Pierzchała, Katarzyna; Grosse, Jocelyn; Mclin, Valérie Anne; Cudalbu, Cristina

doi:10.1016/j.jhep.2019.05.022

Cited by 60 publications

(92 citation statements)

References 75 publications

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“…Similarly, the negative correlation of distance moved with plasma bilirubin may be interpreted in one of two ways: either this finding points to bilirubin as a neurotoxin or circulating bilirubin levels serve as a surrogate for severity of liver disease. NH 4 + impacts the CNS both through direct toxicity and indirect metabolic pathways 26,27 , something which we have previously shown in BDL rats 18 . This finding is further supported by studies showing that HE disappeared when GS was blocked experimentally during chronic hyperammonemia 28,29 .…”

Section: Neurometabolic Response To Plasma Ammonium Liver Disease Ismentioning

confidence: 59%

“…+ load which reaches the CNS, where the only detoxifying pathway is the production of Gln by glutamine synthetase (GS) in astrocytes. Eight weeks post-BDL surgery, young BDL rats experienced a 4.5-times increase of Gln in hippocampus, compared to 2.4-times in adult BDL rats 18 (Figs. S2 and S3).…”

Section: Neurometabolic Response To Plasma Ammonium Liver Disease Ismentioning

confidence: 95%

“…Plasma samples were analysed using Reflotron ® System for glucose, Integra ® 400 Plus for ammonium and COBAS ® 8000 for total bilirubin as markers of biliary obstruction and liver function (Roche, Switzerland). 18 , to confirm the presence of motor deficits (characteristic of type C HE) 21,22 .…”

Section: H-mrs Studies In Patients Withmentioning

confidence: 99%

“…In vivo 1 H-MRS. In vivo 1 H-MRS was performed as previously described 18 . Measurements were conducted on a horizontal 9.4 T MR-system using SPECIAL sequence (TE = 2.8 ms) in a volume of interest (2 × 2.8 × 2 mm 3 ) placed in dorsal hippocampus.…”

Section: Behavioural Tests Locomotor Activity Was Assessed In the Opmentioning

confidence: 99%

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Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease

Račkayová

Braissant

Rougemont

et al. 2020

Sci Rep

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type c hepatic encephalopathy (type c He) is increasingly suspected in children with chronic liver disease (CLD), and believed to underlie long-term neurocognitive difficulties. The molecular underpinnings of type c He in both adults and children are incompletely understood. in the present study we combined the experimental advantages of in vivo high field 1 H magnetic resonance spectroscopy with immunohistochemistry to follow longitudinally over 8 weeks the neurometabolic changes in the hippocampus of animals having undergone bile duct ligation as pups. Rats who develop cLD early in life displayed pronounced neurometabolic changes in the hippocampus characterized by a progressive increase in glutamine concentration which correlated with plasma ammonia levels and a rapid decrease in brain myo-inositol. Other neurometabolic findings included a decrease in other organic osmolytes (taurine, choline-containing compounds and creatine), ascorbate and glutamate. At the cellular level, we observed an increase in glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression in the hippocampus at 4 weeks post bile duct ligation (BDL), together with astrocytic morphological alterations. These findings differ from observations in the brain of adult rats following BDL, and are in keeping with the commonly accepted theory of age-dependent vulnerability.

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Section: Neurometabolic Response To Plasma Ammonium Liver Disease Ismentioning

confidence: 59%

Section: Neurometabolic Response To Plasma Ammonium Liver Disease Ismentioning

confidence: 95%

Section: H-mrs Studies In Patients Withmentioning

confidence: 99%

Section: Behavioural Tests Locomotor Activity Was Assessed In the Opmentioning

confidence: 99%

See 2 more Smart Citations

Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease

Račkayová

Braissant

Rougemont

et al. 2020

Sci Rep

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“…Recently, a study using MR-spectroscopy with a high field (9.4 Tesla) was able to detect a large number of individual compounds in brains of rats with chronic liver disease. 13 In the near future, such non-invasive techniques will probably be able to identify the composition of the CSF by putting a specific voxel in the lateral ventricles. Unfortunately, presently, it is not possible to evaluate the BBB or the blood-CSF barrier permeability at bedside.…”

mentioning

confidence: 99%

Plasmatic osmolality and hepatic encephalopathy: A new player on the field?

Weiss

Rose

2020

Liver International

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The blood-brain barrier (BBB), the interface between the blood and the brain, is a highly regulated assembly of cells. As a result, osmotic gradients exist across the BBB which dictates the direction of water diffusion. Cerebral oedema is a result of brain hypertonicity and increasing non-permeable molecules in the blood can help draw water from the brain. However, this will theoretically only occur when the BBB is intact, non-impaired. Clinically, identifying BBB breakdown remains very challenging. Plasmatic osmolarity is defined as the

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Neurometabolism and brain morphometry in an adolescent female with an extra‐hepatic congenital portosystemic shunt

Chabbey,

Cudalbu,

Barras

et al. 2023

JPGN rep.

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BackgroundChronic hepatic encephalopathy (CHE) has been reported both in patients with congenital porto‐systemic shunts (CPSS) and chronic liver disease. CHE is difficult to recognize in children as there is no clear definition and its manifestations are highly variable. CHE is associated with variations in brain volumes and metabolites that have already been demonstrated using 1.5‐3T MRI systems. However, the in‐depth study of brain metabolism requires the high spectral resolution of high magnetic fields.Objectives and MethodsWe analyzed the neurometabolic profile, brain volumes and T1 relaxation times of a child with a CPSS using high field proton magnetic resonance spectroscopy (1H MRS, 7T) combined with MRI and compared it to an age‐matched control group. We also evaluated the impact of shunt closure on neurocognitive symptoms using adapted neuropsychological tests.Results7T MRS revealed a significant increase in glutamine compared to controls, a decrease in brain osmolytes, and a slight elevation in NAA concentrations. 7T MRI scans showed morphological abnormalities but no changes in the signal intensity of the globus pallidus. Neurocognitive testing revealed attention deficit disorder, language difficulties, and mild intellectual disability. Most of these areas improved after shunt closure.ConclusionsIn this paediatric case of type B HE with normal fasting ammonia, neurometabolic profile was compatible with what has been previously shown in chronic liver disease, while also demonstrating an isolated glutamine peak. In addition, neurocognitive function partially improved after shunt closure, arguing strongly for shunt closure in both presymptomatic and symptomatic patients.

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Longitudinal neurometabolic changes in the hippocampus of a rat model of chronic hepatic encephalopathy

Cited by 60 publications

References 75 publications

Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease

Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease

Plasmatic osmolality and hepatic encephalopathy: A new player on the field?

Neurometabolism and brain morphometry in an adolescent female with an extra‐hepatic congenital portosystemic shunt

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