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

Račkayová, Veronika; Braissant, Olivier; Rougemont, Anne‐Laure; Cudalbu, Cristina; Mclin, Valérie Anne

doi:10.1038/s41598-020-64416-3

Cited by 13 publications

(23 citation statements)

References 53 publications

(80 reference statements)

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“…Experimental models with rats developing chronic liver disease early in life have demonstrated pronounced neurometabolic changes. 18 Early onset of liver disease in children has been associated with neurocognitive impairment. 1,[13][14][15]19,20 Malnutrition may contribute, and impaired growth has been identified as a predictor of poor neurocognitive -2021…”

Section: Discussionmentioning

confidence: 99%

Impaired Neurocognitive Performance in Children after Liver Transplantation

Østensen

Skarbø

Sanengen

et al. 2022

The Journal of Pediatrics

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Objectives To assess longitudinal neurocognitive development after liver transplantation and evaluate factors associated with neurocognitive performance.Study design Data from neurocognitive testing of 65 children (aged <18 years) who underwent liver transplantation at Oslo University Hospital between 1995 and 2018 were collected from the testing program after transplantation. The parent-reported version of the Behavior Rating Inventory of Executive Function was used to assess executive function.Results A total of 104 neurocognitive tests were conducted on 65 patients. At the first test, conducted at a median of 4.1 years (IQR, 1.5-5.3 years) after transplantation and at a median age of 6.7 years (IQR, 5.4-10.5 years), the mean full-scale IQ (FSIQ) was 91.7 AE 14, and the mean verbal comprehension index was 92.0 AE 14.5. In the 30 patients tested more than once, there was no significant difference in FSIQ between the first test at a median age of 5.8 years (IQR, 5.2-8.5 years) and the last test at a median age of 10.8 years (IQR, 9.8-12.9 years) (87.4 AE 12.9 vs 88.5 AE 13.2; P = .58). Compared with the patients who underwent transplantation a age >1 year (n = 35), those who did so at age <1 year (n = 30) had a lower FSIQ (87.1 AE 12.6 vs 96.6 AE 13.8; P = .005) and lower verbal comprehension index (87.3 AE 13.8 vs 95.4 AE 13.0; P = .020). Age at transplantation (P = .005; adjusted for cholestasis: P = .038) and transfusion of >80 mL/kg (P = .004; adjusted for age at transplantation: P = .046) were associated with FSIQ.Conclusions Young age at transplantation and large blood transfusions during transplantation are risk factors for poor neurocognitive performance later in life. Children who undergo transplantation before 1 year of age have significantly lower neurocognitive performance compared with those who do so later in childhood. Cognitive performance did not improve over time after transplantation.

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Section: Discussionmentioning

confidence: 99%

Impaired Neurocognitive Performance in Children after Liver Transplantation

Østensen

Skarbø

Sanengen

et al. 2022

The Journal of Pediatrics

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“…In this context, ligation of the bile‐duct can also be performed in young rats (i.e. 15 or 21 days after birth) leading to a model of type C HE in the developing brain 152 Differences between gender in children with biliary atresia have been observed, 153 with more women presenting with cholestatic liver disease than men.…”

Section: Current Animal Models Of Hementioning

confidence: 99%

2021 ISHEN guidelines on animal models of hepatic encephalopathy

DeMorrow

Cudalbu

Davies

et al. 2021

Liver International

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This working group of the International Society of Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) was commissioned to summarize and update current efforts in the development and characterization of animal models of hepatic encephalopathy (HE). As defined in humans, HE in animal models is based on the underlying degree and severity of liver pathology. Although hyperammonemia remains the key focus in the pathogenesis of HE, other factors associated with HE have been identified, together with recommended animal models, to help explore the pathogenesis and pathophysiological mechanisms of HE. While numerous methods to induce liver failure and disease exist, less have been characterized with neurological and neurobehavioural impairments. Moreover, there still remains a paucity of adequate animal models of Type C HE induced by alcohol, viruses and non‐alcoholic fatty liver disease; the most common etiologies of chronic liver disease.

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“…For instance, cirrhotic patients who died from hepatic coma had reduced glutamate concentration in brain regions associated with HE [123,131]. Similarly, studies in cirrhotic-BDL rats have shown that glutamate concentration depletion in the hippocampus was correlated with systemic ammonia levels [132]. Overall, disrupted glutamate homeostasis has been well documented in HE, however the implications of glutamate excitotoxicity in neuronal cell death remains poorly defined.…”

Section: Healthy Astrocyte = Healthy Neuronmentioning

confidence: 99%

Hepatic Encephalopathy: From Metabolic to Neurodegenerative

2021

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Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of both acute and chronic liver disease. As a metabolic disorder, HE is considered to be reversible and therefore is expected to resolve following the replacement of the diseased liver with a healthy liver. However, persisting neurological complications are observed in up to 47% of transplanted patients. Several retrospective studies have shown that patients with a history of HE, particularly overt-HE, had persistent neurological complications even after liver transplantation (LT). These enduring neurological conditions significantly affect patient's quality of life and continue to add to the economic burden of chronic liver disease on health care systems. This review discusses the journey of the brain through the progression of liver disease, entering the invasive surgical procedure of LT and the conditions associated with the post-transplant period. In particular, it will discuss the vulnerability of the HE brain to peri-operative factors and post-LT conditions which may explain non-resolved neurological impairment following LT. In addition, the review will provide evidence; (i) supporting overt-HE impacts on neurological complications post-LT; (ii) that overt-HE leads to permanent neuronal injury and (iii) the pathophysiological role of ammonia toxicity on astrocyte and neuronal injury/damage. Together, these findings will provide new insights on the underlying mechanisms leading to neurological complications post-LT.

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

Cited by 13 publications

References 53 publications

Impaired Neurocognitive Performance in Children after Liver Transplantation

Impaired Neurocognitive Performance in Children after Liver Transplantation

2021 ISHEN guidelines on animal models of hepatic encephalopathy

Hepatic Encephalopathy: From Metabolic to Neurodegenerative

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