Metabolic brain disease最新文献

{"title":"Ginsenoside CK modulates glucose metabolism via PPARγ to ameliorate SCOP-induced cognitive dysfunction.","authors":"Na Li, Xingyu Fang, Hui Li, Jian Liu, Nan Chen, Xiaohui Zhao, Qing Yang, Xijun Chen","doi":"10.1007/s11011-025-01596-9","DOIUrl":"https://doi.org/10.1007/s11011-025-01596-9","url":null,"abstract":"<p><p>Ginsenoside compound K (CK) exhibits neuroprotective properties; however, the underlying mechanisms behind these effects have not been investigated thoroughly. CK is the primary active compound derived from ginseng and is metabolized in the gut. It enhances neuronal function by modulating the gut microflora. Therefore, the present study aimed to elucidate the mechanism through which CK enhances cognitive function, employing gut microbiome and microarray analyses. The results revealed that CK upregulated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), suppressed amyloid-β (Aβ) aggregation in hippocampal neurons, and influenced the expression of cyclin-dependent kinase-5 (CDK5), (including insulin receptor substrate 2) IRS2, insulin-degrading enzyme (IDE), glycogen synthase kinase-3 beta (GSK-3β), glucose transporter type 1 (GLUT1), and glucose transporter type 3 (GLUT3) proteins. These proteins play crucial roles in regulating brain glucose metabolism, increasing neuronal energy, and reducing neuronal apoptosis, thereby ameliorating cognitive impairment in mice.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"168"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772440","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":"Ursolic acid derivatives improved clinical signs of experimental autoimmune encephalomyelitis by modulating central nervous system inflammation.","authors":"Elaine Carlos Scherrer, Karla Antunes Ramos, Ydia Mariele Valadares, Igor Gabriel Machado Soares, Alessandra Paula Carli, Fernando Sá Silva, Jeferson Gomes Silva, Daniel Gomes Alvarenga, Alessa Sin Singer Brugiolo, Rodrigo Moreira Verly, Maiara Rodrigues Salvador, Angelo Marcio Leite Denadai, Caio César Souza Alves, Sandra Bertelli Ribeiro Castro","doi":"10.1007/s11011-025-01591-0","DOIUrl":"https://doi.org/10.1007/s11011-025-01591-0","url":null,"abstract":"<p><p>The immunopathogenesis of multiple sclerosis (MS) involves the activation of T lymphocytes, leading to progressive axonal loss and brain atrophy. Ursolic acid (AU) has been widely used as an herbal medicine, with the ability to inhibit the production and secretion of cytokines and may influence the differentiation of CD4 + helper cells. In this study, we aimed to investigate the immunomodulatory effects of ursolic acid derivatives (methyl 3β-hydroxyurs-12-en-28-oate (AUD1) and methyl 3β-acetoxyurs-12-en-28-oate (AUD2)) in a model of experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous immunization of myelin oligodendrocyte glycoprotein peptide (MOG_35-55) in C57BL/6 mice. On the 15th day post-induction (dpi), the mice were treated with AU, AUD1, or AUD2 (50 mg/kg intraperitoneally per day) for six days. Clinical signs were monitored until 21 dpi, and parameters were assessed in the spinal cord, lymph nodes, and brain at 21 dpi. The results showed that both derivatives similarly attenuated the clinical signs of EAE and reduced inflammation and demyelination in the spinal cord. In addition, they reduced the number of pro-inflammatory cells in the brain, the level of IL-1β, TNF, and IFN-γ in the spinal cord, and, in the periphery, promoted the regulation of pro-inflammatory cells. In conclusion, regulating cells in the periphery and reducing the number of pro-inflammatory cells in the CNS, with AUD1 and AUD2, culminated in the efficacy of the clinical parameters presented in EAE, suggesting a therapeutic potential for treating MS.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"166"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753497","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":"Ferroptosis and Alzheimer's: unveiling new avenues for the treatment and prevention.","authors":"Veerta Sharma, Prateek Sharma, Thakur Gurjeet Singh","doi":"10.1007/s11011-025-01587-w","DOIUrl":"https://doi.org/10.1007/s11011-025-01587-w","url":null,"abstract":"<p><p>Alzheimer's disease (AD), one of the most prevalent neurodegenerative illnesses worldwide, has a devastating effect on individual, families and society. Despite the extensive research and effort, various clinical trials aimed against amyloid-β, which is suspected to have a causative role in the illness, have not yet shown any clinically significant success to date. Emerging evidence suggests that ferroptosis, a kind of programmed cell death triggered by lipid peroxidation and dependent on iron, plays a role in AD. There is a complex relationship between AD and ferroptosis. In both the processes iron dysregulation, altered anti-oxidant mechanisms and lipid peroxidation is involved. Ferroptotic processes contributes to the neuro-inflammation, oxidative stress and damage to the neurons as observed in AD. Additionally, amyloid-β, a hallmark of AD, may influence the ferroptosis, further linked the two pathways. Numerous signalling pathways such as Phospho inositide 3-kinase, Glycogen synthase kinase-3β, 5'-AMP-activated protein kinase, nuclear factor erythroid 2-related factor-2 and Sirtuin pathway plays a part in the pathophysiology of AD. Through a comprehensive review of current research and experimentation, this investigation elucidates the interactions between novel pharmacological agents (ferroptotic inhibitors) and AD-related pathways. Furthermore, this review highlights the various ferroptotic inhibitors as the therapeutic agents for the slowing down the progression of AD. The crosstalk between these processes could unveil the potential therapeutic targets for the AD treatment.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"167"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753496","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":"Protective effects of alpha-lipoic acid on memory deficit induced by repeated doses of solifenacin in mice: the role of nitro-oxidative stress.","authors":"Leonardo Pimentel Dantas, Emanuel Carneiro de Vasconcelos, Carla da Silva Cunha, Pauliane Valeska Chagas Batista, Morgana Carla Souza Torres, Caren Nádia Soares de Sousa, Gabriel Angelo de Aquino, Manuel Alves Dos Santos Junior, Pedro Henrique Freitas de Rezende, Wilson Silva de Vasconcelos, Manoel Cláudio Azevedo Patrocinio, Silvânia Maria Mendes Vasconcelos","doi":"10.1007/s11011-025-01586-x","DOIUrl":"https://doi.org/10.1007/s11011-025-01586-x","url":null,"abstract":"<p><p>Solifenacin (Sol) is one of the most used antimuscarinics for the treatment of bladder dysfunction and there are no conclusive studies on its effects on learning and memory after long-term use. Since substances with antioxidant action, such as alpha-lipoic acid (ALA), have shown protective action in memory deficit and Alzheimer's disease, we decided to study the effects of Sol alone or associated with ALA in behavioral tests of memory and its relation to nitro-oxidative stress in different brain areas. Mice received saline or Sol p.o. for 14 or 28 days. ALA groups received: (a) saline + ALA, (b) Sol for 14 days and Sol + ALA from the 15th to the 28th days and, (c) Sol + ALA for 28 days. Behavioral tests were performed and oxidative changes (lipid peroxidation) and nitrite in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were also determined. Sol produced memory alterations in the mice, reducing the step-down latency and the recognition index in the novel object recognition test. Sol also increased lipid peroxidation in PFC, HC and ST and nitrite levels in the HC. On the other hand, ALA associated with Sol was able to restrict the effects caused by Sol alone, both in relation to nitro-oxidative parameters and in relation to behavioral tests. Taken together, our data suggest that ALA can be administered as an adjunctive drug in patients requiring prolonged use of Sol to mitigate these adverse central nervous system effects. However, clinical studies need to be performed to corroborate preclinical research.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"165"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735969","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":"Sex-specific modulation of FOLR1 and its cycle enzyme genes in Alzheimer's disease brain regions.","authors":"Cristina Sanfilippo, Paola Castrogiovanni, Rosa Imbesi, Michele Vecchio, Manlio Vinciguerra, Kaj Blennow, Henrik Zetterberg, Michelino Di Rosa","doi":"10.1007/s11011-025-01578-x","DOIUrl":"https://doi.org/10.1007/s11011-025-01578-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive and functional decline. Its incidence increases significantly with age and is more prevalent in women than men. We investigated the folate receptor alpha (FOLR1) gene expression levels in the central nervous system (CNS) of AD and non-demented healthy control (NDHC) subjects. Our cohort included 3,946 samples: 2,391 NDHC and 1,555 AD patients, stratified by brain region, age, and sex. Interestingly, a significant increase in FOLR1 expression was observed only in females with AD compared to NDHC females. Furthermore, we found that FOLR1 expression was differentially increased in the prefrontal cortex (PFC) and diencephalon (DIE) only in AD females. Moreover, in females, genes involved in the folic acid (FA) cycle that drives DNA synthesis were significantly modulated. In contrast, in males, downregulation of TYMS effectively blocks the completion of the cycle, thereby preventing downstream DNA synthesis. Tissue Transcriptome Deconvolution (TTD) analysis revealed astrocytes and endothelial cells associated with FOLR1 expression in both AD males and females. Gene Ontology analysis supported these findings, showing enrichment in processes aligned with these cell types. Positive correlations between brain FOLR1 expression and markers for astrocytes (glial fibrillary acidic protein) and endothelial cells (CD31) provided further validation. Our findings suggest a potential role for sex-dependent FOLR1 expression and its association with specific brain regions and cellular processes in AD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"163"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735986","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":"Amomum tsao-ko crevost et lemaire ameliorates depression-like behaviors and hippocampal inflammation by inhibiting microglia activation and HMGB1/TLR4/NF-κB pathway in diabetic mice with depression.","authors":"Zhen Wang, Huilin Ren, Caixia Wang, Ruixue Min, Yue Ma, Yanli Ma, Xiaofeng Zhang","doi":"10.1007/s11011-025-01592-z","DOIUrl":"https://doi.org/10.1007/s11011-025-01592-z","url":null,"abstract":"<p><p>Diabetic depression may be closely related to hippocampal inflammation. We hypothesized that Amomum tsao-ko Crevost et Lemaire (A. tsao-ko) might ameliorate depression-like behavior and glucose intolerance by modulating hippocampal inflammation. UPLC-Q-Exactive-MS/MS was used to identified the constituents in the ethanol extract of A. tsao-ko (EEAT). Then a diabetic depression (DD) model was established and treated for 4 weeks. Depression-like behaviors were assessed using the open field test, sucrose preference test and tail suspension test. The neuronal injury was observed by hematoxylin-eosin staining and Nissl staining. Oral glucose tolerance test, fasting blood glucose, hemoglobin Alc, fasting insulin and homeostasis model assessment of insulin resistance were used to evaluate the effects of EEAT on glucose metabolism. Serum lipids, neurotransmitters, neuroendocrine and inflammation levels were detected by biochemical kits and enzyme-linked immunosorbent assay. Activation of microglia markers was detected by immunofluorescence. Western blotting was used to detect the effect of EEAT on the HMGB1/TLR4/NF-κB protein expression. 48 chemical components were identified from EEAT. Animal experiments showed that EEAT improved the levels of glucose and lipid metabolism, alleviated depression-like behaviors, decreased the level of neurotransmitters and increased the secretion of neuroendocrine-related hormones. The activation of microglia and immunofluorescence intensity of neurogenesis also improved. At the same time, the expression of HMGB1, TLR4 and NF-κB proteins in the inflammatory pathway was also inhibited. EEAT had effects on improving DD symptoms, which may be achieved by down-regulating the HMGB1/TLR4/NF-κB protein expression.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"164"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735965","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":"The beneficial effects of D-allose and D-allulose on the brain under ischemic stroke and obese-insulin resistant conditions: evidence from in vitro to clinical studies.","authors":"Yanmei Huang, Chanisa Thonusin, Masaaki Tokuda, Nipon Chattipakorn, Siriporn C Chattipakorn","doi":"10.1007/s11011-025-01580-3","DOIUrl":"https://doi.org/10.1007/s11011-025-01580-3","url":null,"abstract":"<p><p>Ischemic stroke, and obese-insulin resistance are common pathological conditions that lead to brain injury, resulting in neurodegeneration, brain atrophy, and cognitive dysfunction. Rare sugars, which are scarce monosaccharide in nature, have been investigated as a potential treatment for these adverse conditions. However, the beneficial effects of rare sugars on the brain have never been summarized. Therefore, this article comprehensively summarizes and discusses the benefits of rare sugars on the brain under physiological condition, ischemic stroke, and obese-insulin resistance. The potential mechanisms mediating these benefits of rare sugars are also described. Any contradictory findings are also included. This article adds weight to the impetus for further investigations into the applications of rare sugars as a novel therapeutic paradigm in clinical application.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"162"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735989","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":"Hydroxysafflower yellow A alleviates the inflammatory response in astrocytes following cerebral ischemia by inhibiting the LCN2/STAT3 feedback loop.","authors":"Lijuan Song, Yige Wu, Lijun Yin, Yanzhe Duan, Jianlin Hua, Mengwei Rong, Kexin Liu, Junjun Yin, Dong Ma, Ce Zhang, Baoguo Xiao, Cungen Ma","doi":"10.1007/s11011-025-01581-2","DOIUrl":"https://doi.org/10.1007/s11011-025-01581-2","url":null,"abstract":"<p><p>Lipocalin-2 (LCN2), an acute phase protein mainly expressed in astrocytes (Ast), is closely related to the production of inflammatory cytokines following ischemic stroke. During the pathophysiological process of ischemic stroke, the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is activated. Despite evidence suggesting some link between the two, the relationship between the JAK2/STAT3 signaling pathway and the LCN2 expression in Ast following brain ischemia is incompletely understood. Hydroxysafflower yellow A (HSYA), an active ingredient found in Carthamus tinctorius L flowers, has been demonstrated to effectively mitigate cerebral ischemia via its anti-inflammatory effect. However, whether HSYA mitigates the neuroinflammatory damage after ischemic stroke by disrupting the interaction between the JAK2/STAT3 signaling pathway and LCN2 in Ast is unknown. Focusing on these two scientific questions, we established an in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and in vitro primary astrocyte oxygen glucose deprivation/reperfusion (OGD/R) model. In vivo results showed that HSYA treatment alleviated nerve damage and inhibited the expression of LCN2 and inflammatory factors in Ast. In vitro results showed after OGD/R the expression of LCN2 and inflammatory cytokines increased and the JAK2/STAT3 was activated in Ast. Meanwhile, after OGD/R the JAK2/STAT3 activation in Ast increased LCN2 expression, and the inhibition of LCN2 expression by HSYA decreased the JAK2/STAT3 activation in Ast. These findings suggest that there is an interaction between the LCN2 and JAK2/STAT3 in Ast after ischemic stroke, which can enhance the inflammatory factors and exacerbate neuroinflammatory injury. Therefore, we conclude that HSYA may inhibit the LCN2/STAT3 loop in Ast, thereby mitigating neuroinflammation after cerebral ischemia.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"161"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764340","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":"Luteolin ameliorates ischemic/reperfusion injury by inhibiting ferroptosis.","authors":"Hua Li, Jin-Xia Li, Yi-di Zeng, Cai-Xing Zheng, Si-Si Dai, Jian Yi, Xu-Dong Song, Ting Liu, Wang-Hua Liu","doi":"10.1007/s11011-025-01588-9","DOIUrl":"https://doi.org/10.1007/s11011-025-01588-9","url":null,"abstract":"<p><p>Ischaemic stroke is a large disease burden worldwide. Thrombolysis and thrombectomy are the main treatment methods for cerebral ischemia-reperfusion (I/R) injury. Luteolin, as a flavonoid compound, has an antagonistic effect on inflammation, oxidative stress, and tumorigenesis in disease. Therefore, the primary objective of this study is to determine the role of luteolin in cerebral I/R injury. Oxygen glucose deprivation/reoxygenation (OGD/R)-treated BV2 cells and a cerebral I/R rat model were established. Cell viability and death were verified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide staining. The glutathione/oxidized glutathione (GSH/GSSG) ratio, superoxide dismutase (SOD) activity, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels were determined using corresponding kits. Solute Carrier Family 7 Member 11 (SLC7A11), nuclear transcription factor erythroid 2-related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) levels were analyzed by western blotting. In addition, the infarct volume of brain tissues was examined by tetrazolium chloride (TTC) staining. Luteolin treatment significantly enhanced cell viability, decreased LDH release and intracellular ROS and MDA levels, and increased the GSH/GSSG ratio and SOD activity in OGD/R-treated BV2 cells. PI staining demonstrated that cell death was inhibited after luteolin treatment. Additionally, luteolin treatment significantly increased the SLC7A11, NRF2, and GPX4 protein levels. After treatment with ML385, an NRF2 inhibitor, the influence of luteolin on OGD/R-treated BV2 cells was reversed. Moreover, luteolin treatment significantly decreased the neurological score and infarct area in the brain tissues of cerebral I/R rats. Our research demonstrated that luteolin treatment inhibited ferroptosis by enhancing antioxidant functions through the NRF2 pathway, which provides a promising method for treating cerebral I/R injury.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"159"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730671","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":"Artesunate alleviated hippocampal neuron pyroptosis by down-regulating NLRP3 in rats with cerebral small vessel disease.","authors":"Xiaokun Wang, Hequan Zhong, Xiangyu Kong, Hongqiao Wei, Bing Li","doi":"10.1007/s11011-025-01590-1","DOIUrl":"10.1007/s11011-025-01590-1","url":null,"abstract":"<p><p>Our study aims to investigate the potential of artesunate (ART) in improving learning and memory function by down-regulating NLRP3 and consequently affecting pyroptosis levels in the brains of rats with cerebral small vessel disease (CSVD). Initially, Sprague-Dawley (SD) rats were randomly assigned to five groups: the solvent sham operation group, solvent model group, low-dose ART (ART_L) group, medium-dose ART (ART_M) group, and high-dose ART group (ART_H). CSVD rat models were established through bilateral common carotid artery occlusion (BCCAO). Subsequently, the rats were further divided into four groups: the empty plasmid control group (shNC) and three groups receiving NLRP3-shRNA interference plasmids (shNLRP3-1, shNLRP3-2, shNLRP3-3). We recorded animal behaviors and stained nerve cell changes. Hippocampal expression levels of Caspase-1, cleaved caspase-1, IL-18, IL-1β, GSDMD-N, β-actin, and NLRP3 were evaluated in each group. Our findings revealed that ART ameliorated cognitive dysfunction and brain tissue injury in CSVD rats. Moreover, expression levels of cleaved caspase-1, IL-18, IL-1β, GSDMD-N, and NLRP3 in the hippocampus were significantly reduced in the shNLRP3 group, resulting in improved cognitive function in these rats. These results suggest that NLRP3 could be a potential therapeutic target in CSVD development in rats, and modulating its expression might mitigate pathological alterations associated with CSVD. Subsequently, lipopolysaccharide (LPS) was injected into the tail vein, and inflammatory factors in peripheral blood of rats were found to be increased, suggesting that the level of intracranial NLRP3 was increased. In addition, MWM experiment showed that after the increase of NLRP3 expression, the repair effect of ART on learning and memory dysfunction was weakened. ART may enhance cognitive impairment in CSVD rats by downregulating NLRP3 expression in the brain, thereby inhibiting neuronal cell pyroptosis in the hippocampus.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"160"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730770","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}