Kinetic deterioration of short memory in rat with acute hepatic encephalopathy: Involvement of astroglial and neuronal dysfunctions

Khiat, Abdelaati El; Tamegart, Lahcen; Draoui, Ahmed; Fari, Radouane El; Sellami, Souad; Rais, Hanane; Hiba, Omar El; Gamrani, Halima

doi:10.1016/j.bbr.2019.03.046

Cited by 17 publications

(10 citation statements)

References 57 publications

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“…Dysfunction of 5-HT receptor and excess serotonergic brain activity is involved in HE development (Apelqvist et al, 1998;Dhanda and Sandhir, 2015;Khiat et al, 2019). In hyperammonemia mice, the 5-HT2B receptor was found to be up-regulated in the brain and had no response to 5-HT.…”

Section: -Hydroxytryptaminementioning

confidence: 99%

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Chen

Ruan

et al. 2021

Front. Cell. Infect. Microbiol.

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Hepatic encephalopathy (HE) is a neurological disorder that occurs in patients with liver insufficiency. However, its pathogenesis has not been fully elucidated. Pharmacotherapy is the main therapeutic option for HE. It targets the pathogenesis of HE by reducing ammonia levels, improving neurotransmitter signal transduction, and modulating intestinal microbiota. Compared to healthy individuals, the intestinal microbiota of patients with liver disease is significantly different and is associated with the occurrence of HE. Moreover, intestinal microbiota is closely associated with multiple links in the pathogenesis of HE, including the theory of ammonia intoxication, bile acid circulation, GABA-ergic tone hypothesis, and neuroinflammation, which contribute to cognitive and motor disorders in patients. Restoring the homeostasis of intestinal bacteria or providing specific probiotics has significant effects on neurological disorders in HE. Therefore, this review aims at elucidating the potential microbial mechanisms and metabolic effects in the progression of HE through the gut–brain axis and its potential role as a therapeutic target in HE.

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Section: -Hydroxytryptaminementioning

confidence: 99%

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Chen

Ruan

et al. 2021

Front. Cell. Infect. Microbiol.

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“…As stated above, astrocytes are involved in the progression of HE and some authors even propose that HE is primarily a glyopathy (Norenberg, 1996;El Khiat et al, 2019) as these cells are responsible for most of the ammonium and glutamate detoxification. This process, however, consumes a significant amount of glucose to produce glutamine and absorb two ammonia molecules which can lead to a decrease in glucose oxidation to CO 2 .…”

Section: Discussionmentioning

confidence: 99%

Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats

Guazzelli

Cittolin-Santos

Meira-Martins

et al. 2020

Front. Mol. Neurosci.

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Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, playing a role in the development of HE. The purpose of the present study is to investigate early alterations in redox status, energy metabolism and astrocytic reactivity of rats submitted to ALF. Adult male Wistar rats were submitted either to subtotal hepatectomy (92% of liver mass) or sham operation to induce ALF. Twenty-four hours after the surgery, animals with ALF presented higher plasmatic levels of ammonia, lactate, ALT and AST and lower levels of glucose than the animals in the sham group. Animals with ALF presented several astrocytic morphological alterations indicating astrocytic reactivity. The ALF group also presented higher mitochondrial oxygen consumption, higher enzymatic activity and higher ATP levels in the brain (frontoparietal cortex). Moreover, ALF induced an increase in glutamate oxidation concomitant with a decrease in glucose and lactate oxidation. The increase in brain energy metabolism caused by astrocytic reactivity resulted in augmented levels of reactive oxygen species (ROS) and Poly [ADP-ribose] polymerase 1 (PARP1) and a decreased activity of the enzymes superoxide dismutase and glutathione peroxidase (GSH-Px). These findings suggest that in the early stages of ALF the brain presents a hypermetabolic state, oxidative stress and astrocytic reactivity, which could be in part sustained by an increase in mitochondrial oxidation of glutamate.

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“…Increased blood ammonia levels have been considered as the main pathophysiological mechanism of HE [41,42] by causing swelling astrocytes, activation of microglia and neuroin ammation [43][44][45][46][47][48][49][50]. Microglia activation can promote the proliferation and release of pro-in ammatory cytokines [50], and the in ammation state can eventually lead to neuronal death [51].…”

Section: Discussionmentioning

confidence: 99%

Reduced Serum Cholinesterase Activity Distinguishes Hepatic Encephalopathy From 48 Types of Human Diseases

Rong¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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Background: Hepatic encephalopathy is a complication of central nervous systems due to liver failure-related brain inflammation. Less than half of patients suffering from liver failure develop hepatic encephalopathy, which suggests other factors beyond liver failure might contribute to hepatic encephalopathy. Indeed, we reported previously that the levels of serum direct bilirubin, a liver cell-made product, are counter-intuitively highest in hepatic encephalopathy patients among 72 clinically defined diseases. In current study, we tested if cholinesterase could serve as a biomarker for hepatic encephalopathy by comparing serum cholinesterase activities among 48 different types of human diseases.Methods: The activity of serum cholinesterase was determined by the standard “continuous monitoring method” in the clinical laboratory of the hospital where the serum cholinesterase activities from 137,305 independent tests with 48 clinically defined diseases and 3,387 independent tests from healthy individuals who came to the hospital for physical examination during the past 5 years were retrieved. All data were analyzed with RStudio V.1.3.1073 and python libraries 3.8.Results: We found that all 48 types of diseases had decreased cholinesterase activity compared to control based on either mean or median values. Remarkably, hepatic encephalopathy had the lowest cholinesterase activity and the serum cholinesterase activity was the best biomarker for hepatic encephalopathy (AUC 0.99, sensitivity 100%, and specificity 99%) among all diseases. Moreover, two component analysis of cholinesterase activity distributions revealed hepatic encephalopathy resembled preeclampsia and uremia whereas cirrhosis resembled multiple myeloma, leukemia, myeloproliferative disorder, and liver cancer.Conclusions: Decreased cholinesterase activity was an almost perfect serum biomarker for patients suffering hepatic encephalopathy at all stages. The resemblance of hepatic encephalopathy to preeclampsia and uremia based on cholinesterase activities provided new insight in understanding hepatic encephalopathy etiology beyond liver failure.

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Kinetic deterioration of short memory in rat with acute hepatic encephalopathy: Involvement of astroglial and neuronal dysfunctions

Cited by 17 publications

References 57 publications

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats

Reduced Serum Cholinesterase Activity Distinguishes Hepatic Encephalopathy From 48 Types of Human Diseases

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