Metabolic brain disease最新文献

{"title":"Hypercholesterolemia, oxidative stress, and low-grade inflammation: a potentially dangerous scenario to blood-brain barrier.","authors":"Hémelin Resende Farias, Lílian Corrêa Costa-Beber, Fátima Theresinha Costa Rodrigues Guma, Jade de Oliveira","doi":"10.1007/s11011-025-01620-y","DOIUrl":"10.1007/s11011-025-01620-y","url":null,"abstract":"<p><p>For more than a century, hypercholesterolemia has been linked to atherosclerotic cardiovascular disease. Notably, this metabolic condition has also been pointed out as a risk factor for neurodegenerative diseases, such as Alzheimer's disease (AD). Oxidative stress seems to be the connective factor between hypercholesterolemia and cardio and neurological disorders. By disturbing redox homeostasis, hypercholesterolemia impairs nitric oxide (NO) availability, an essential vasoprotective element, and jeopardizes endothelial function and selective permeability. The central nervous system (CNS) is partially protected from peripheral insults due to an arrangement between endothelial cells, astrocytes, microglia, and pericytes that form the blood-brain barrier (BBB). The endothelial dysfunction related to hypercholesterolemia increases the risk of developing cardiovascular diseases and also initiates BBB breakdown, which is a cause of brain damage characterized by neuroinflammation, oxidative stress, mitochondrial dysfunction, and, ultimately, neuronal and synaptic impairment. In this regard, we reviewed the mechanisms by which hypercholesterolemia-induced oxidative stress affects peripheral vessels, BBB, and leads to memory deficits. Finally, we suggest oxidative stress as the missing link between hypercholesterolemia and dementia.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"205"},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tong-Qiao-Huo-Xue Decoction mitigates post-stroke inflammatory response via suppression of the FIB-NLRP3 signaling pathway.","authors":"Ping Huang, Hao Sun, Yan Wang, Ning Wang","doi":"10.1007/s11011-025-01633-7","DOIUrl":"10.1007/s11011-025-01633-7","url":null,"abstract":"<p><strong>Background: </strong> The post-stroke inflammatory response denotes the inflammatory damage inflicted upon brain tissue following stroke. Plasma fibrinogen (FIB) can permeate the compromised blood-brain barrier (BBB) after ischemic stroke, leading to the activation of the NLRP3 inflammasome. Tong-Qiao-Huo-Xue-Decoction (TQHXD), a traditional formula used to promote blood circulation and resolve blood stasis, has shown potential in this context. Nevertheless, the precise therapeutic mechanisms of TQHXD in mitigating cerebral ischemia-reperfusion injury remain to be fully elucidated. Objective. To examine the reparative effects and underlying mechanisms of TQHXD-CSF on inflammatory damage in BV-2 cells subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) injury. Methods. To establish an in vitro model of OGD/R injury and an inflammatory BV-2 cells model induced by FIB. The protective effects of TQHXD-CSF on OGD/R-injured cells were verified using CCK-8 and LDH assays. Immunofluorescence, SEM, Western blotting, and CHIP-PCR were employed to confirm that TQHXD reduces the inflammatory response by downregulating FIB levels. Pull-down and co-immunoprecipitation (CO-IP) assays were conducted to detect the interaction between FIB and NLRP3. Results. TQHXD-CSF can significantly inhibit the abnormal increase in LDH levels induced by OGD/R, enhance cell viability, and mitigate cell pyroptosis. Additionally, TQHXD-CSF reversed the marked upregulation of FIB, NLRP3, and GSDMD fluorescence intensity and protein expression caused by the FIB inflammation model, demonstrating an effect comparable to that of lumbrokinase, a fibrinolytic agent for FIB. Furthermore, it notably reduced the acetylation of H3 and H4 in the NLRP3 promoter. Importantly, the pull-down and CO-IP results indicated a robust binding affinity between FIB and NLRP3. Conclusion. TQHXD-CSF can inhibit inflammation by downregulating the FIB-NLRP3 pathway and exert a protective effect on BV-2 cells under OGD/R and FIB inflammatory injury.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"206"},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial activation as a hallmark of neuroinflammation in Alzheimer's disease.","authors":"Rasoul Ebrahimi, Shahrzad Shahrokhi Nejad, Mahdi Falah Tafti, Zahra Karimi, Seyyedeh Reyhaneh Sadr, Dana Ramadhan Hussein, Niki Talebian, Khadijeh Esmaeilpour","doi":"10.1007/s11011-025-01631-9","DOIUrl":"10.1007/s11011-025-01631-9","url":null,"abstract":"<p><p>Microglial activation has emerged as a hallmark of neuroinflammation in Alzheimer's disease (AD). Central to this process is the formation and accumulation of amyloid beta (Aβ) peptide and neurofibrillary tangles, both of which contribute to synaptic dysfunction and neuronal cell death. Aβ oligomers trigger microglial activation, leading to the release of pro-inflammatory cytokines, which further exacerbates neuroinflammation and neuronal damage. Importantly, the presence of activated microglia surrounding amyloid plaques is correlated with heightened production of cytokines such as interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), creating a vicious cycle of inflammation. While microglia play a protective role by clearing Aβ plaques during the early stages of AD, their chronic activation can lead to detrimental outcomes, including enhanced tau pathology and neuronal apoptosis. Recent studies have highlighted the dualistic nature of microglial activation, showcasing both inflammatory (M1) and anti-inflammatory (M2) phenotypes that fluctuate based on the surrounding microenvironment. Disruption in microglial function and regulation can lead to neurovascular dysfunction, further contributing to the cognitive decline seen in AD. Moreover, emerging biomarkers and imaging techniques are unveiling the complexity of microglial responses in AD, providing avenues for targeted therapeutics aimed at modulating these cells. Understanding the intricate interplay between microglia, Aβ, and tau pathology is vital for developing potential interventions to mitigate neuroinflammation and its impact on cognitive decline in AD. This review synthesizes current findings regarding microglial activation and its implications for AD pathogenesis, offering insights into future therapeutic strategies.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"207"},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvianolic acid B ameliorates Aβ42 toxicity in Aβ42-expressing Drosophila model: behavioral and transcriptomic profiling.","authors":"Florence Hui Ping Tan, Ghows Azzam, Nazalan Najimudin, Shaharum Shamsuddin, Azalina Zainuddin, Mohd Shareduwan Mohd Kasihmuddin","doi":"10.1007/s11011-025-01625-7","DOIUrl":"10.1007/s11011-025-01625-7","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. It is characterized by the accumulation of amyloid-beta (Aβ) plaques in which Aβ42 is the most toxic and aggressive species. This work investigates the possibility of salvianolic acid B (SalB), a natural compound with established neuroprotective activity, to counteract the Aβ42-induced toxicity in a Drosophila melanogaster model of AD. SalB's effect was assessed in the Aβ42-expressing Drosophila model by measuring three major AD-related behavioural symptoms: eye morphology (cytotoxicity), lifespan, and locomotor activity. The eye assay, longevity, and locomotion assays were employed, followed by RNA sequencing (RNA-seq) to identify molecular alterations following SalB treatment. Aβ42 expression in the Aβ42-expressing Drosophila model resulted in deformed eye morphology, reduced lifespan, and motor impairment. Treatment with SalB restored part of eye morphology, extended lifespan, and improved locomotion. RNA-seq revealed differential gene expression in oxidative phosphorylation, glutathione metabolism, and detoxification processes, suggesting the involvement of antioxidant defence in SalB-mediated neuroprotection. These findings indicate that SalB could be therapeutic for AD and other neurodegenerative disorders, possibly through the modulation of oxidative stress against Aβ42 toxicity. Further research is warranted to address its mechanisms and other uses in neurodegenerative therapy.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"204"},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin level regulators may affect cognitive ability caused by motion sickness: an experimental study.","authors":"Mengyu Zhong, Jian Zhu, Bohan Zhang, Hui Shen, Hongxia Li, Yuxiao Tang, Shuang Nie, Fengfeng Mo","doi":"10.1007/s11011-025-01630-w","DOIUrl":"10.1007/s11011-025-01630-w","url":null,"abstract":"<p><p>Abnormal acceleration induced motion sickness (MS) and elevated blood glucose levels, showing obviously cognitive impairments. The mechanism of cognitive impairment caused by MS is still unclear. Here, blood metabolite detection, insulin level regulators, stress hormones, cytokines and MS assessment were conducted for the population and MS model rats, correlation analysis of motion sickness index (MSI) and above factors were conducted by correlation analysis. We found glucose after acceleration was positively correlated with Graybiel's score. Insulin and leptin levels decreased, while ghrelin level increased after acceleration in both human and rat groups. We injected insulin level regulators into rats before being exposed to acceleration, the results showed that MSI of the insulin group (INS) was significantly lower than rotation group (ROT), streptozotocin group (STZ) and streptozotocin & insulin group (SINS). MSI in STZ was higher than ROT and INS. Rats injected with ghrelin showed higher MSI than the control group and ghrelin antagonist group. Acceleration stimulation induced phosphorylation of insulin receptor substrate 1 (IRS1) and expression of synaptic protein in hippocampus. We also found that the insulin microinjection into hippocampus prevented MS symptoms and cognitive ability as measured by the MSI, the Open Field Test, the T-maze, and the Morris water maze. Our study indicates that insulin and insulin level regulators can affect MS symptoms and cognitive ability.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"203"},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS-responsive dextran-benzeneboronic acid pinacol ester micelles encapsulating edaravone for the treatment and mechanism of cerebral ischemia-reperfusion injury.","authors":"Hexiang Zhao, Ping Yang, Mou Zhang, Wenshu Zheng, Renli Qi, Xiaofeng Zhu, Jinghui Li, Shipeng Li","doi":"10.1007/s11011-025-01626-6","DOIUrl":"10.1007/s11011-025-01626-6","url":null,"abstract":"<p><p>Reperfusion, while essential for restoring blood supply, paradoxically exacerbates neuronal damage through cerebral ischemia-reperfusion injury (CIRI). This study aimed to develop a reactive oxygen species (ROS)-responsive drug delivery system (DDS) loaded with edaravone (EDA) to enhance targeted therapy for CIRI. The stimuli-responsive DDS was synthesized using dextran (DEX) as the biocompatible carrier and benzeneboronic acid pinacol ester (BAPE) as the ROS-sensitive moiety. The physicochemical characteristics of the DEX-BAPE/EDA (DB/EDA) micelles were systematically evaluated. In vitro studies assessed the anti-inflammatory, antioxidant, and anti-apoptotic effects of DB/EDA. Moreover, the neuroprotective efficacy of DB/EDA in vivo was analyzed via behavioral tests, infarct volume measurement, ELISA assays of inflammatory cytokines and OS markers, and Western blot analysis of Nrf2-related pathways. Pharmacokinetics and biosafety were analyzed through plasma profiling and H&E staining. DB/EDA exhibited high stability, efficient drug encapsulation, and ROS-responsive drug release. Cellular uptake studies confirmed enhanced internalization of DB/EDA micelles in BV2 cells. In the oxygen-glucose deprivation/reoxygenation (OGD/R) model, DB/EDA significantly suppressed TNF-α, IL-1β, IL-6, and MDA, restored SOD levels, and attenuated apoptosis. In the middle cerebral artery occlusion/reperfusion (MCAO/R) mice, DB/EDA administration effectively improves cognition and mitigates neuronal damage. Mechanistically, DB/EDA activated the Nrf2/HO-1 pathway, amplifying antioxidant and anti-inflammatory responses. Pharmacokinetic analysis revealed prolonged circulation and increased brain accumulation, and histopathological analysis demonstrated the safety profile of DB/EDA. The ROS-responsive DB/EDA nano-micelles provided targeted EDA delivery to ischemic brain regions, alleviating CIRI via Nrf2 activation, suggesting that DB/EDA is a promising strategy for CIRI treatment.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"202"},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MEG3 promotes pyroptosis via miR-145-5p/TLR4/NLRP3 axis and aggravates cerebral ischemia-reperfusion injury.","authors":"Lei Li, Hao Zha, Wei Miao, Chunyan Li, Aimei Wang, Shiyuan Qin, Shuang Gao, Lingli Sheng, Ying Wang","doi":"10.1007/s11011-025-01613-x","DOIUrl":"10.1007/s11011-025-01613-x","url":null,"abstract":"<p><p>Long noncoding RNA (lncRNA) MEG3 has been considered as a novel target for alleviating the brain tissue damage during cerebral ischemia-reperfusion injury (CIRI). Numerous studies have reported that pyroptosis is involved in the pathogenesis of CIRI. This study focused on whether MEG3 modulates CIRI via pyroptosis and its underlying mechanism. The middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model were established. si-MEG3 and miR-145-5p inhibitor were transfected to inhibit MEG3 and miR-145-5p, respectively. As a TLR4 inhibitor, Resatorvid inhibits the TLR4 signaling pathway. TTC and TUNEL staining were used for infarction volume and cell death detection. The differential expression of MGE3, miR-145-5p, TLR4, NLRP3, Caspase-1, IL-1β, and IL-18 was determined using real-time PCR and western blot. The interaction between MEG3 and miR-145-5p, as well as between miR-145-5p and TLR4 was confirmed by the dual-luciferase reporter assay. This study confirmed that the elevated expression of MEG3 during CIRI, and it contributes to pyroptosis by regulating miR-145-5p/TLR4 axis. The knockdown of MEG3 reduced the expression of TLR4, NLRP3, Caspase-1, IL-1β, and IL-18, thereby preventing pyroptosis. Inhibition of miR-145-5p reversed the effect of MEG3 knockdown and promoted pyroptosis. Resatorvid, the inhibitor of TLR4, counteracted the effect of miR-145-5p inhibitor and suppressed pyroptosis. Our findings reveal that MEG3 promotes pyroptosis via miR-145-5p/TLR4/NLRP3 axis and aggravates CIRI, suggesting a potential therapeutic target for ischemic stroke.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"201"},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the impact of Pomalidomide on memory dysfunction induced by neuroinflammation in Pentylenetetrazole-seizure model of male Wistar rats.","authors":"Elnaz Khorasanian, Hassan Rajabi-Maham, Abdolkarim Hosseini, Vahid Azizi","doi":"10.1007/s11011-025-01622-w","DOIUrl":"10.1007/s11011-025-01622-w","url":null,"abstract":"<p><p>Neuroinflammation, a consequence and cause of epileptic seizures, is one of the leading causes of memory dysfunction in epileptic patients. The; current study evaluated Pomalidomide's; (POM) anti-inflammatory effect on passive avoidance memory impairments caused by Pentylenetetrazole-induced seizure in male Wistar rats. Rats were grouped into five groups, including control, Pentylenetetrazole (PTZ), and treatment groups. Three groups were pretreated with different doses of Pomalidomide (25, 50, and 100 mg/kg) before PTZ 70 (mg/kg). The Shuttle box test was utilized to examine passive avoidance memory and learning. Finally, brain samples were prepared under deep anesthesia and used for histological observation and gene expression studies. Based on data analysis Pomalidomide -pretreated groups showed better memory performance than either the control or the PTZ group (P < 0.05). Also, the anti-inflammatory effects of POM caused the expression of Nuclear Factor Kappa B (NF-kB) and Tumor necrosis factor alpha (Tnf-α) in the hippocampus to decrease significantly compared to the control group (P < 0.05). In addition, histological examinations obtained from H&E staining in the hippocampus also showed the protective effects of the Pomalidomide. The results indicated that Pomalidomide reduced the expression of inflammatory mediators in the hippocampus and has a neuroprotective effect. It seems that in this way it reduces memory impairments caused by acute seizure induction.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"200"},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low carbohydrate and low-calorie diets reduce liver fat and lower brain glutamate and myo-inositol levels in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).","authors":"Andreana P Haley, Jack Knight-Scott, Marie Caillaud, Isabelle Gallagher, Jessica Park, Yanrong Li, Tianyu Wang, Hirofumi Tanaka, Jeffrey D Browning","doi":"10.1007/s11011-025-01624-8","DOIUrl":"10.1007/s11011-025-01624-8","url":null,"abstract":"<p><p>In a longitudinal cohort study with intervention (NCT05216796), we utilized multiorgan imaging to determine if metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with elevated cerebral glutamate and myo-inositol and to determine their sensitivity to dietary intervention. Fifty-five adults with self-reported MASLD or high MASLD risk (3 + metabolic risk factors) received liver and brain magnetic resonance spectroscopy scans pre and post two-week low carbohydrate (≤30 g/d) or low-calorie (women ~ 1200 kcal/d; men ~ 1500 kcal/d) diet, both known for their ability to reduce liver fat. Forty-four adults completed the study (36 female, average age 54 years). Thirty out of 44 met clinical criterion for MASLD based on neuroimaging (≥ 5% hepatic triglycerides). Intervention was associated with significant decreases in liver fat fraction (mean difference = 3.101, 95% CI 2.104-4.099, p < 0.0001), glutamate (mean difference = 0.753, 95% CI 0.274-1.233, p = 0.0032) and myo-inositol (mean difference = 0.478, 95% CI 0.180-0.775, p = 0.0027) in patients with confirmed MASLD. Thus, MASLD may be a source of glutamate neurotoxicity and neuroinflammation and diet is an effective strategy for supporting brain as well as liver health.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"199"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic encephalopathy in cirrhosis: therapies and developments.","authors":"Ajay Kumar Mishra, Radha Krishan Dhiman","doi":"10.1007/s11011-025-01598-7","DOIUrl":"10.1007/s11011-025-01598-7","url":null,"abstract":"<p><p>Hepatic encephalopathy (HE) is a frequent decompensation in patients with cirrhosis, which significantly affects morbidity and mortality. Ammonia is a major neurotoxin implicated in the pathogenesis, progression, and severity of HE, and various organs including the gut, muscle, kidney, and brain are involved in its metabolism. Therefore, therapeutic management involves reducing ammonia production and increasing its elimination from the blood and the brain. Prevention of HE in patients at high risk of first and recurrent episodes is important for prolonging survival. Various anti-ammonia therapies with synergistic and complementary actions have been attempted for overt HE and for prophylaxis of the first and recurrent episodes of HE. In the current review, we summarize the currently used and under-development pharmacotherapies/procedure(s) for HE in cirrhosis and their mechanism of action. Primary and secondary prophylaxis with monotherapies and combination therapies are also discussed.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"198"},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}