Animal models and experimental medicine最新文献

{"title":"Animal models for investigating post-stroke cognitive impairment: A neurovascular trafficking perspective.","authors":"Pratchaya Kaewkaen","doi":"10.1002/ame2.70315","DOIUrl":"10.1002/ame2.70315","url":null,"abstract":"<p><p>Post-stroke cognitive impairment (PSCI) is a major cause of long-term disability after ischemic stroke, yet its mechanisms remain incompletely explained by infarct volume, lesion location, or conventional vascular risk factors alone. Animal models are indispensable for clarifying how ischemic injury evolves into delayed cognitive dysfunction and for determining which mechanisms are experimentally tractable, reproducible, and translationally relevant. This review examines PSCI from a neurovascular trafficking perspective, focusing on how laboratory animal models can be used to investigate secretory pathway stress, endolysosomal dysfunction, autophagy-lysosomal flux, extracellular vesicle signaling, blood-brain barrier disruption, glial reactivity, myelin debris clearance, white matter injury, and cognition-relevant behavioral phenotypes. Rodent models of transient or permanent middle cerebral artery occlusion, photothrombotic stroke, embolic stroke, chronic cerebral hypoperfusion, bilateral carotid artery stenosis, and subcortical white-matter injury each reproduce selected components of the human PSCI spectrum. No single model fully captures the temporal, vascular, cellular, and cognitive complexity of human PSCI; therefore, model selection should be driven by the mechanistic question, disease phase, vascular pathology, cellular compartment, cognitive domain, and welfare burden under investigation. The central argument is not that neurovascular trafficking failure is already a proven causal pathway, but that well-designed animal studies can test, refine, or falsify this hypothesis. Future studies should integrate model validity, translational rigor, and welfare refinement through longitudinal cognitive testing, multimodal imaging, cell-specific molecular profiling, extracellular vesicle phenotyping, intervention-based validation, randomization, blinding, sample-size justification, humane endpoints, perioperative care, and transparent reporting.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded characterization of the valproic acid zebrafish larval model of autism spectrum disorder: Insights into dysregulation in the gut.","authors":"Lesha Pretorius, Johanna Adriana Coetzee, Alexio Pedro Dos Santos, Carine Smith","doi":"10.1002/ame2.70303","DOIUrl":"10.1002/ame2.70303","url":null,"abstract":"<p><strong>Background: </strong>Relative lack of data on mechanisms underpinning poor gastrointestinal (GI) health in autism spectrum disorder (ASD) limits patient management strategies. Although the valproic acid (VPA) model of ASD is widely used, a comprehensive profile of the model in zebrafish is still lacking, and almost no data are available on ASD-like GI symptomology or underlying mechanisms.</p><p><strong>Methods: </strong>ASD-like craniofacial morphology, anxiety-like behavior, GI anatomical and functional dysregulation, and dysregulation of the monoaminergic system in both the brain and the gut were simultaneously assessed in zebrafish larvae at 7 days postfertilization.</p><p><strong>Results: </strong>VPA exposure was associated with increased intraocular distance, neuroligin 3 (NLGN3) dysregulation, decreased muscle tone, and an anxious phenotype (increased thigmotaxis and dark zone preference [light-dark preference test]). In the brain, protein expression levels of tryptophan hydroxylase 2 (TPH2) and serotonin (5-HT), but not serotonin transporter (SERT), were downregulated, as well as tyrosine hydroxylase (TH) and dopamine transporter (DAT), whereas dopamine (DA) was upregulated. In the gut, upregulated serotonergic (increased TPH1 and 5-HT) and downregulated dopaminergic (decreased TH, increased DAT) protein expression was linked to thinner-walled, longer intestinal tracts, and decreased spontaneous peristaltic activity.</p><p><strong>Conclusions: </strong>Dopaminergic dysregulation aligns with the ASD literature. Novel findings include an association of hyposerotonergic tone with anxiety-like outcomes as core symptomology in ASD. Furthermore, we demonstrate compartment-specific dopaminergic and serotonergic dysregulation in the gut, which provides support for relatively decreased gut motility in ASD.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCA1 deficiency-induced cholesterol accumulation aggravates colonic epithelial injury in knockout hamsters.","authors":"Chang Liu, Jingjie Zheng, Sijing Shi, Jianwen Chen, Geroge Liu, Wei Huang, Xunde Xian, Yuhui Wang, Jianglin Fan, Ping Zhu, Xiawen Yang","doi":"10.1002/ame2.70301","DOIUrl":"10.1002/ame2.70301","url":null,"abstract":"<p><strong>Background: </strong>ATP-binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux, yet its role in inflammatory bowel disease (IBD) remains incompletely understood. This study investigated the consequences of intestinal epithelial cholesterol accumulation-primarily driven by ABCA1 deficiency-on colonic inflammation and the underlying molecular mechanisms.</p><p><strong>Methods: </strong>ABCA1 knockout (KO) and wild-type (WT) Syrian golden hamsters were fed a high-cholesterol high-fat diet for 12 weeks. Colon specimens were analyzed for pathological changes, inflammatory markers, cholesterol accumulation, and gene expression profiles. Furthermore, in vitro experiments were performed using the human colon epithelial cell line Caco-2.</p><p><strong>Results: </strong>ABCA1 deficiency, in the context of a high-cholesterol high-fat diet, triggered significant colonic inflammation in KO hamsters, characterized by epithelial damage, inflammatory cell infiltration, and elevated pro-inflammatory cytokine levels. These pathological changes were associated with impaired mucosal barrier integrity, a four-fold increase in epithelial cholesterol accumulation, and reduced E-cadherin, ZO-1 and occludin expression. Furthermore, ABCA1 deficiency promoted oxidative stress and induced marked remodeling of the gut microbiota.</p><p><strong>Conclusions: </strong>Our findings establish a pathogenic role for ABCA1 deficiency in driving colonic epithelial injury and inflammation, suggesting that ABCA1 may play an important role in the pathogenesis of IBD.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Baseline podocyte-associated state and persistent cell-matrix transcriptional programs are associated with BALB/c substrain differences in adriamycin nephropathy\".","authors":"","doi":"10.1002/ame2.70320","DOIUrl":"10.1002/ame2.70320","url":null,"abstract":"","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal models of anemia of inflammation: Methodological advances, limitations, and translational applications.","authors":"Jiayi Cheng, Xiaodi Zhou, Qian Liu, Zixian Liu, Hao Wu","doi":"10.1002/ame2.70304","DOIUrl":"10.1002/ame2.70304","url":null,"abstract":"<p><p>Anemia of inflammation (AI) represents one of the most prevalent secondary anemias in clinical practice, frequently complicating a wide spectrum of chronic inflammatory diseases. Given its highly heterogeneous etiology and complex pathophysiological mechanisms, the establishment of rational and high-fidelity animal models is vital for elucidating the core mechanisms of AI and optimizing clinical diagnostic and therapeutic strategies. This narrative review provides a structured categorization of current AI animal models into three major paradigms: sterile inflammation models, disease-specific models, and genetically engineered models. We provide an in-depth comparative analysis of their underlying modeling principles, methodological protocols, and characteristic phenotypic profiles, while comprehensively evaluating their respective translational advantages and intrinsic limitations. Furthermore, we discuss the prospective applications of these models in deciphering pathomechanisms, validating therapeutic targets, and developing interventional strategies. To enhance reproducibility and translational relevance, we propose a streamlined phenotyping panel and a model selection framework. The precise selection and rational application of these tailored models will contribute to improved reliability of fundamental AI research and accelerate its translational progression from bench to bedside.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A self-retaining mouth prop for intraoral access during periodontal surgery in rat models: A technical note.","authors":"Saravanan Sampoornam Pape Reddy, Delfin Lovelina Francis, Vivek Kumar Thakur, Balaji Manohar, Shaili Pradhan, Shesh Rai","doi":"10.1002/ame2.70300","DOIUrl":"10.1002/ame2.70300","url":null,"abstract":"<p><strong>Background: </strong>Rodent models are widely used in oral health research; however, maintaining stable and effective intraoral retraction in the small oral cavity is challenging. Manual retraction methods often lead to procedural instability, operator fatigue, and increased tissue trauma during rodent oral surgery.</p><p><strong>Methods: </strong>A stainless-steel wire mouth prop incorporating helices for self-retention and auxiliary lateral soft tissue displacement prongs was fabricated. 32 adult Wistar albino rats were randomly allocated to two groups (n = 16 each). In the experimental group, procedures were performed using a custom mouth prop, and the control group underwent conventional manual retraction. Outcomes included time to achieve adequate retraction, slippage events per procedure, operator fatigue scores, and complication rates. Student's t-test was used for statistical analysis of retraction time, and the Mann-Whitney U test was used for slippage frequency, and fatigue scores. Statistical significance was determined using a Bonferroni-adjusted threshold of p < 0.017.</p><p><strong>Results: </strong>Retraction time was significantly shorter in the experimental group (2.5 ± 0.6 min) than in control group (6.3 ± 1.2 min, p < 0.001). Slippage events per procedure were markedly lower with mouth prop (0.1 vs. 3.4 ± 1.1, p < 0.001). Operator fatigue scores were also reduced (2.4 ± 0.8 vs. 7.2 ± 1.4, p < 0.001). Complication rates were significantly lower in the experimental group (p = 0.024).</p><p><strong>Conclusion: </strong>The proposed custom-made mouth prop demonstrated favorable procedural handling characteristics during rat intraoral surgery and may serve as a practical, low-cost refinement tool for improving intraoral access and procedural stabilization in experimental oral research settings.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baihe Zhimu Decoction ameliorates anxious depression via PI3K/AKT/mTOR pathway-mediated neuroprotection and inhibition of hippocampal neuronal apoptosis.","authors":"Yuanshan Han, Kexin He, Haolan Yang, Jiacheng Dai, Ronglin Chen, Yang Liu, Yuhong Wang, Lin Tang, Hongqing Zhao","doi":"10.1002/ame2.70295","DOIUrl":"10.1002/ame2.70295","url":null,"abstract":"<p><strong>Background: </strong>Anxious depression involves severe emotional dysregulation with a high risk of relapse and suicide. Although the classical Traditional Chinese Medicine formula Baihe Zhimu Decoction (BZD) is widely used for affective disorders, its underlying mechanisms remain poorly understood.</p><p><strong>Methods: </strong>In this study, the chemical constituents of BZD were first identified using UPLC-Q-TOF-MS/MS, followed by a maximum-dose safety evaluation. The therapeutic effects of BZD were then investigated in an anxious-depression mouse model induced by chronic restraint stress (CRS) combined with corticosterone (CORT) administration. Behavioral assessments, including the open field test (OFT), elevated plus maze (EPM), sucrose preference test (SPT), and forced swim test (FST), were performed, together with histopathological examination of hippocampal tissues. Network pharmacology was employed to analyze the relationships between active compounds and potential targets and to predict related signaling pathways. Subsequently, western blot analysis, immunofluorescence staining, Hoechst staining, and flow cytometry, combined with pathway-specific inhibitors, were used to examine the involvement of the signaling pathway in hippocampal tissues and primary hippocampal neurons.</p><p><strong>Results: </strong>Forty-one constituents were identified in BZD. In vivo results showed that BZD significantly alleviated hippocampal pathological injury and improved anxiety- and depression-like behaviors in stressed mice. Network pharmacology analysis identified 19 active compounds and 622 potential targets, highlighting the PI3K/AKT/mTOR signaling pathway. Mechanistically, BZD activated this pathway and protected against neuronal injury, while these effects were attenuated by the PI3K inhibitor LY294002.</p><p><strong>Conclusions: </strong>BZD exerts potent neuroprotective and therapeutic effects against anxious depression, primarily driven by activating the PI3K/AKT/mTOR pathway and preserving hippocampal neuronal integrity.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining a preclinical model of viral myocarditis in accordance with biotech standards","authors":"Jonas Stewen,&nbsp;Julia Riedesel,&nbsp;Juliane Stein,&nbsp;Brandon H. Greene,&nbsp;Svenja Rohde,&nbsp;Sonja Suess,&nbsp;Bjoern Keiner,&nbsp;Priya Panjwani,&nbsp;Padmapriya Ponnuswamy,&nbsp;Juan E. Camacho Londoño","doi":"10.1002/ame2.70263","DOIUrl":"10.1002/ame2.70263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Viral myocarditis is a clinically relevant inflammatory heart disease that can progress to dilated cardiomyopathy and heart failure. However, preclinical models often suffer from limited translational relevance and high animal burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study aimed to refine a murine model of Coxsackievirus B3 (CVB3)-induced myocarditis by integrating dietary and imaging innovations to improve animal welfare, data quality, and clinical applicability. BALB/cJ mice were infected with heart-passaged CVB3 and monitored for up to 56 days. A hydrolyzed amino acid diet was introduced to mitigate CVB3-induced pancreatitis and associated weight loss. Cardiac function was assessed using 1D, 2D, and 4D echocardiography, including speckle-tracking strain analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The refined diet significantly reduced animal health burden, reduced weight loss, and stabilized blood glucose, during development of cardiac inflammation and fibrosis. 4D echocardiography provided a highly sensitive and reproducible detection of systolic dysfunction, while strain analysis revealed early and regional myocardial impairment, closely mirroring clinical myocarditis phenotypes. Histopathological and AI-based analyses confirmed dose- and time-dependent inflammation and fibrosis, with peak inflammation at day 7 and persistent abnormalities through day 56.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, this model offers a robust and ethically optimized platform for translational research and therapeutic development in inflammatory cardiomyopathies, aligned with the principles of the 3Rs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1712-1728"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SDPR–STK38 axis controls the proliferation–differentiation balance in alveolar type II cells","authors":"Jie Wang,&nbsp;Xuepei Lei,&nbsp;Yiying Huang,&nbsp;Jiaming Tang,&nbsp;Guiying Shi,&nbsp;Hang Li,&nbsp;Lin Bai","doi":"10.1002/ame2.70204","DOIUrl":"10.1002/ame2.70204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alveolar type II (AT2) cells act as progenitors that sustain gas exchange and drive postinjury repair. Disruption of their proliferation–differentiation balance promotes pulmonary fibrosis and acute respiratory distress syndrome, but the core regulatory mechanisms are unclear. Serum deprivation response protein (SDPR, cavin-2), a caveolae-associated protein involved in proliferation and lipid metabolism, may modulate AT2 fate. This study investigated how the SDPR–STK38 axis regulates AT2 proliferation and differentiation and its impact on lung homeostasis and regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SDPR knockout (SDPR⁻^/⁻) mice and wild-type littermates were used to evaluate alveolar structure, AT2/AT1 composition, and lung function at baseline and after LPS-induced acute lung injury. Histology, immunostaining, and lung function tests were combined with mass spectrometry and co-immunoprecipitation to identify SDPR-interacting proteins. Gain- and loss-of-function assays in lung tissues and cells were used to assess how SDPR and STK38 regulate GSK-3β/cyclin D1 signaling and Notch–Hes1–dependent AT2 differentiation. Data were analyzed using standard statistical tests appropriate for the experimental design.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SDPR deficiency disrupted alveolar architecture and impaired lung function, accompanied by excessive AT2 expansion and reduced differentiation into AT1 cells. Proteomic and biochemical analyses identified STK38 as a novel SDPR-binding protein. SDPR loss increased STK38 expression, enhanced GSK-3β/cyclin D1 signaling, and promoted AT2 proliferation, while simultaneously reducing Hes1 expression, impairing vacuole formation, and attenuating AT2 differentiation. In the LPS model, SDPR⁻^/⁻ mice developed more severe pathological injury and declined lung function compared to wild-type controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The SDPR–STK38 axis coordinately controls the proliferation–differentiation balance of AT2 cells via GSK-3β/cyclin D1 and Notch–Hes1 signaling. SDPR deficiency drives aberrant AT2 expansion, blocks differentiation toward AT1 cells, and aggravates acute lung injury, highlighting this pathway as a potential therapeutic target for promoting alveolar regeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1813-1827"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine monophosphate–activated protein kinase activation is associated with suppression of NLRP3 inflammasome–mediated neuroinflammation in a weight-drop model of traumatic brain injury in Sprague–Dawley rats","authors":"Triveni Kodi,&nbsp;Paka Sravan Kumar,&nbsp;Krishnadas Nandakumar,&nbsp;Anoop Kishore","doi":"10.1002/ame2.70288","DOIUrl":"10.1002/ame2.70288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) disrupts adenosine monophosphate–activated protein kinase (AMPK) signaling, impairs energy homeostasis, activates inflammatory pathways, and triggers neuroinflammation. AMPK activators such as metformin (MET), quercetin (QUE), resveratrol (RES), cinnamaldehyde (CIN), and berberine (BER) exhibit anti-inflammatory and neuroprotective properties. However, their role in modulating the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome in TBI-induced neuroinflammation remains unclear. This study investigated the neuroprotective effects of AMPK activators in the weight-drop model of TBI, focusing on suppression of the NLRP3 inflammasome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rats received an intraperitoneal administration of AMPK activators—MET (100 mg/kg), QUE (15 mg/kg), RES (25 mg/kg), CIN (25 mg/kg), or BER (50 mg/kg)—from days −3 to 17. TBI was induced on day 1 using the weight-drop method (240 g from 1.5 m). Cognitive performance was evaluated using the novel object recognition test and Morris water maze. Neuroinflammatory markers, including nuclear factor kappa B (NF-κB), NLRP3, pro-caspase-1, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and microglial polarization markers (CD86 and CD206), were assessed using Western blotting and enzyme-linked immunosorbent assay (ELISA). Oxidative stress and histopathological changes were also examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TBI resulted in cognitive impairment, oxidative stress, and neuronal damage; reduced p-AMPK/AMPK ratio; decreased CD206 levels; and elevated the levels of NF-κB, CD86, TNF-α, and NLRP3 inflammasome components (NLRP3, pro-caspase-1, and IL-1β). Pretreatment with AMPK activators significantly improved cognitive deficits, attenuated oxidative stress and neuroinflammation, restored p-AMPK/AMPK ratio, promoted anti-inflammatory effects, and suppressed NLRP3 inflammasome activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AMPK activators exhibited neuroprotection in TBI by improving cognition and regulating oxidative stress, microglial activation, and NLRP3-mediated neuroinflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1849-1868"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}