Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation

Leone, Paola; Mincheva, Gergana; Balzano, Tiziano; Malaguarnera, M; Felipo, Vicente; Llansola, Marta

doi:10.3390/biomedicines10061263

Cited by 14 publications

(6 citation statements)

References 100 publications

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“…Visuospatial memory and learning impairments are a known feature of experimental rodent [68], as well as human, MASH [5]. In our study, we observed a long-term decrease in spatial memory, as shown in the SATM test, but no change in object-recognition memory.…”

Section: Discussionsupporting

confidence: 62%

Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis

Prikhodko,

Matuzok,

Karev

et al. 2024

Livers

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Non-alcoholic metabolic-associated steatohepatitis (MASH) is a condition characterized by increasingly high prevalence and incidence, and also represents an important unmet medical need when it comes to effective pharmacotherapy. In this work, we aimed to explore the therapeutic possibilities of the synergistic combined use of glycyrrhizinic acid (GA) and phosphatidylcholine (PC) to prevent experimental MASH. Adult C57Bl/6 mice were used to model dietary/toxic MASH and treated orally by either GA (34.3 mg/kg/d) or a GA + PC combination (34.3 + 158.1 mg/kg/d) for 3 months. Animal locomotion, behaviour, short-term memory, physical performance, neuromuscular joint function, blood biochemistry, and oxidative stress marker levels were evaluated, followed by histological examination of the liver, skeletal muscle and sciatic nerve with tissue ammonia and lipid content determination. Real-time polymerase chain reaction was used to measure the relative expression of several pathogenetic transcript markers. GA and PC showed moderate additive synergism in their anti-inflammatory, antioxidant, hypoammonaemic, hypoglycaemic, and pro-cognitive activities. Differential effects of the agents were seen in regard to anxiety- and depression-like behaviour as well as gene expression. Our results indicate partial pharmacological synergism between GA and PC and validate further research of its potential clinical applications.

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Section: Discussionsupporting

confidence: 62%

Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis

Prikhodko,

Matuzok,

Karev

et al. 2024

Livers

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“…This finding is supported by other studies of HE models. In the type C HE model induced by carbon tetrachloride (CCl4), microglia activation and increased pro-inflammatory cytokines in the CA1 region of the hippocampus were noted, along with spatial learning and memory impairments [73]. More importantly, chronic hyperammonemia was shown to induce neuroinflammation in the hippocampus [4].…”

Section: Discussionmentioning

confidence: 99%

Short Working Memory Impairment Associated with Hippocampal Microglia Activation in Chronic Hepatic Encephalopathy

El-Mansoury,

Smimih,

El Khiat

et al. 2024

Metabolites

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Hepatic encephalopathy (HE) is a major neuropsychological condition that occursas a result of impaired liver function. It is frequently observed in patients with advanced liver disease or cirrhosis. Memory impairment is among the symptoms of HE; the pathophysiologic mechanism for this enervating condition remains unclear. However, it is possible that neuroinflammation may be involved, as recent studies have emphasized such phenomena. Therefore, the aim of the present study is to assess short working memory (SWM) and examine the involvement of microglia in a chronic model of HE. The study was carried out with male Wistar rats that were induced by repeated thioacetamide (TAA) administration (100 mg/kg i.p injection for 10 days). SWM function was assessed through Y-maze, T-Maze, and novel object recognition (NOR) tests, together with an immunofluorescence study of microglia activation within the hippocampal areas. Our data showed impaired SWM in TAA-treated rats that was associated with microglial activation in the three hippocampal regions, and which contributed to cognitive impairment.

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“…Another study conducted in rat models of MHE with mild liver damage similar to non-alcoholic fatty liver disease (NAFLD) [ 107 ] showed hippocampal neuroinflammation with consequent spatial learning and memory impairment. Increase in CCL2 levels in the hippocampus could be an early event that promotes microglia activation and monocytes infiltration, with their conversion in macrophages.…”

Section: Intestinal Microbiota Modulation As Treatment Strategy and E...mentioning

confidence: 99%

Gut Microbiota and Neuroinflammation in Acute Liver Failure and Chronic Liver Disease

et al. 2023

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Acute liver failure and chronic liver disease are associated with a wide spectrum of neurological changes, of which the best known is hepatic encephalopathy (HE). Historically, hyperammonemia, causing astrocyte swelling and cerebral oedema, was considered the main etiological factor in the pathogenesis of cerebral dysfunction in patients with acute and/or chronic liver disease. However, recent studies demonstrated a key role of neuroinflammation in the development of neurological complications in this setting. Neuroinflammation is characterized by activation of microglial cells and brain secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, which alter neurotransmission, leading to cognitive and motor dysfunction. Changes in the gut microbiota resulting from liver disease play a crucial role in the pathogenesis of neuroinflammation. Dysbiosis and altered intestinal permeability, resulting in bacterial translocation and endotoxemia, are responsible for systemic inflammation, which can spread to brain tissue and trigger neuroinflammation. In addition, metabolites derived from the gut microbiota can act on the central nervous system and facilitate the development of neurological complications, exacerbating clinical manifestations. Thus, strategies aimed at modulating the gut microbiota may be effective therapeutic weapons. In this review, we summarize the current knowledge on the role of the gut–liver–brain axis in the pathogenesis of neurological dysfunction associated with liver disease, with a particular focus on neuroinflammation. In addition, we highlight emerging therapeutic approaches targeting the gut microbiota and inflammation in this clinical setting.

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Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation

Cited by 14 publications

References 100 publications

Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis

Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis

Short Working Memory Impairment Associated with Hippocampal Microglia Activation in Chronic Hepatic Encephalopathy

Gut Microbiota and Neuroinflammation in Acute Liver Failure and Chronic Liver Disease

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