Animal models and experimental medicine最新文献

{"title":"The liver-brain axis: A multidimensional regulatory network implicated in Alzheimer's disease pathogenesis and clinical implications","authors":"Ning Zhang,&nbsp;Wei Chen,&nbsp;Meng Wang","doi":"10.1002/ame2.70262","DOIUrl":"10.1002/ame2.70262","url":null,"abstract":"<p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition. The liver-brain axis underscores the central role of the liver in modulating cognitive function through multidimensional regulatory mechanisms. As a core metabolic and detoxification organ, the liver also helps maintain cerebral homeostasis via pathways including the urea cycle, antioxidant systems, ketone body metabolism, and bile acid regulation. Dysfunction of these processes may lead to ammonia accumulation, exacerbated oxidative stress, and Aβ clearance, thereby accelerating the pathological progression of AD. Liver-derived factors such as apolipoprotein E (APOE), C-reactive protein (CRP), fibroblast growth factor 21 (FGF21), and insulin-like growth factor 1 (IGF-1) significantly increase the risk of AD through dual mechanisms-inhibiting Aβ clearance and activating neuroinflammation, thereby directly affecting cognitive function via modulation of inflammation, metabolism, and blood–brain barrier (BBB) integrity. Neural interfaces formed by the hypothalamic–pituitary-target gland axis and the vagus nerve enable communication from the liver to the brain, with emerging evidence also supporting a reverse influence from the brain to the liver. Emerging technologies such as molecular tracing and nanocarriers provide new tools for deciphering dynamic interactions within the liver-brain axis. Liver-targeted metabolic interventions show potential for reversing cognitive impairment. Unlike previous reviews that mainly focused on single pathways, this review conceptualizes the liver-brain axis as a multidimensional regulatory network in AD. By clearly linking network nodes to potential therapeutic interventions, it provides us with a novel framework that not only describes the various mechanisms but also focuses on identifying actionable targets for disease prevention and treatment.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1743-1760"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537529","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":"Identification of senescence-related genes in Parkinson's disease reveals candidate therapeutic targets and pathological processes","authors":"Haojie Wu,&nbsp;Tingting Liu,&nbsp;Xiangshu Cheng,&nbsp;Jianshe Wei","doi":"10.1002/ame2.70240","DOIUrl":"10.1002/ame2.70240","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD), a progressive neurodegenerative disease, is closely linked to the aging process; however, its precise molecular mechanisms remain unclear. This work aimed at clarifying the function of senescence-related genes (SRGs) in PD and investigating their molecular underpinnings, as well as their potential diagnostic and therapeutic significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By integrating bioinformatics with experimental validation, the CellAge database provided 278 SRGs for this study. A total of 2925 differentially expressed genes (DEGs) and 31 differentially expressed SRGs (DESRGs) were identified, which are mainly involved in signaling pathways, including nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and interleukin 17 (IL-17). Through protein–protein interaction (PPI) network analysis, 10 hub genes were identified, such as <i>IRF7</i>, <i>IFNG</i>, and <i>BCL6</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In PD mouse and MN9D cell models by D-galactose (D-gal) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), combined treatment (D-gal + MPTP) synergistically reduced tyrosine hydroxylase (TH) expression, promoted α-synuclein (α-syn) aggregation, aggravated cellular senescence, and caused significant upregulation of <i>IRF7</i>, whereas <i>IRF7</i> small interfering RNA (siRNA) intervention reversed senescence- and PD-related pathological changes. Molecular docking analyses identified candidate small molecules targeting hub genes, including fostamatinib and ropsacitinib. In vitro experiments provided preliminary support that these compounds modulated SYK and TYK2 proteins and alleviated pathological phenotypes in cellular models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, this study demonstrates that D-gal-induced aging-like stress accelerates PD-related pathological progression by activating multiple signaling pathways, including JAK–STAT, AGE–RAGE, and NF-κB, thereby promoting inflammation, oxidative stress, and neuronal dysfunction. Key genes including <i>IRF7</i> may serve as candidate biomarkers, providing preliminary evidence for the role of senescence-like stress in PD pathogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1761-1781"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364319","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":"Molecular mechanism of Xanthotoxol against gastric cancer: A comprehensive study integrating network pharmacology, computer simulations, and experimental validation.","authors":"Yi Yang, Yu-Hua Du, Chuang Song, Lan-Nv Ma, Lin Luo, De-Xu Xu, Xiao-Yan Ma, Zi-Ying Zhou, Yi Nan, Yi Yang, Ling Yuan","doi":"10.1002/ame2.70234","DOIUrl":"10.1002/ame2.70234","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a prevalent malignant tumor of the digestive system worldwide. Xanthotoxol (Xan), a natural compound extracted from traditional Chinese medicine such as Angelica archangelica, has demonstrated antitumor properties. However, its specific effects on GC remain unreported.</p><p><strong>Methods: </strong>Hub targets of Xan in GC were identified by integrating weighted gene co-expression network analysis (WGCNA) with network pharmacology. Molecular docking and molecular dynamics (MD) simulations were conducted to analyze the interaction between the hub targets and Xan. The effects of Xan on GC cell proliferation, cell cycle, apoptosis, migration, and invasion were examined using cell experiments and xenograft tumor model. Histopathological evaluation of changes in tumor and liver tissues was performed after Xan intervention. Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were employed to analyze hub target expression and clarify Xan's molecular mechanism against GC.</p><p><strong>Results: </strong>A total of six hub genes highly correlated with GC were identified (MMP12, KDR, CCND1, PDGFRB, PLAU, and PLK1). Molecular docking and MD simulations revealed a significant binding affinity between Xan and hub genes. Experiments demonstrated that Xan inhibited proliferation, cell cycle, migration, and invasion while promoting apoptosis. Xan could alleviate liver injury caused by subcutaneous tumor in mice. Furthermore, Xan upregulated MMP12 expression and downregulated KDR, CCND1, PDGFRB, PLAU, and PLK1 in GC cells.</p><p><strong>Conclusions: </strong>Xan shows promise as a GC treatment by modulating MMP12, KDR, CCND1, PDGFRB, PLAU, and PLK1 expression, which inhibits proliferation, cell cycle, migration, and invasion, while enhancing apoptosis and reducing liver damage.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149752","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":"Aortic valve disease: Novel animal models for advancing our understanding of the underlying mechanisms.","authors":"Liya Hou, Xue Liu, Wangxing Hu, Xianbao Liu, Wei Zhu","doi":"10.1002/ame2.70294","DOIUrl":"10.1002/ame2.70294","url":null,"abstract":"<p><p>The global public health burden of aortic valve disease (AVD) is growing due to its high mortality rate and lack of suitable pharmaceutical therapies in clinical practice, a challenge that is largely attributable to our poor understanding of its complicated underlying mechanisms. A better understanding of the pathological processes underlying AVD is urgently needed to identify novel therapeutic options. Appropriate animal models are emerging as vital tools for basic and translational research, and the development of new models and the important information they have provided has significantly aided our research. However, different animal models have unique limitations in their ability to mimic human AVD pathology. In this review, we summarize the available AVD animal models and provide a detailed description of the major principles underlying each animal model, including methodology, pathological features, and potential use and application in AVD research. Both the advantages and disadvantages of specific models are also carefully highlighted; thus this comprehensive review provides a valuable animal model reference for both basic and preclinical researchers.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070680","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":"Repeated instillations of bleomycin in male mice induce a perivascular remodeling at distance of fibrotic areas in the context of progressive pulmonary fibrosis.","authors":"Céline-Hivda Yegen, Zakaria Maakoul, Dominique Marchant, Patrice Callard, Julia Bourse, Jean-François Bernaudin, Hilario Nunes, Carole Planès, Emilie Boncoeur, Nicolas Voituron","doi":"10.1002/ame2.70247","DOIUrl":"10.1002/ame2.70247","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is the archetypal form of progressive pulmonary fibrosis (PPF), as well as being the most common and severe type of interstitial lung disease. IPF is characterized by progressive, diffuse interstitial remodeling, stiffening of the lung parenchyma and is also most often associated with pulmonary hypertension (PH), which significantly impacts the clinical course and outcome of the disease. To improve targeted therapeutic options and survival predictions, as well as offering an overall better understanding of the disease, researchers need models that best reflect the characteristics observed in patients and allow the study of comorbidities associated with pulmonary fibrosis. Chronic pulmonary fibrosis was induced in male C57BL/6 mice through intratracheal instillation (ITI) of 3 low-doses of bleomycin (BLM) every 2 weeks. Mice were sacrificed 15 or 90 days after the last ITI. Clinical follow-up and histological analysis were performed to study lung and perivascular remodeling. Our results suggest that fractionated bleomycin instillation generates a persistent and progressive pulmonary fibrosis in mice. This is associated with collagen remodeling in the perivascular space outside fibrotic areas. We hypothesize that this remodeling, accompanied by a mild but significant increase in pulmonary artery media thickness, could be a precursor to pulmonary fibrosis-associated hypertension. These results suggest that this model could improve our understanding of pulmonary remodeling and vascular lesions in the early stages of pulmonary fibrosis.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042643","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":"Developing a strain-dependent susceptibility to hepatocellular carcinoma in a murine model based on histopathological evidence and genetic context.","authors":"Osayd Zohud, Aysar Nashef, Imad Abu-Elnaaj, Fuad A Iraqi","doi":"10.1002/ame2.70283","DOIUrl":"10.1002/ame2.70283","url":null,"abstract":"<p><p>Hepatocellular carcinoma is a leading cause of cancer-related mortality worldwide. Smad4, a well-established tumor suppressor within the transforming growth factor-β (TGF-β) signaling pathway, has an oncogenic potential of its heterozygous loss, still poorly defined, especially across genetically diverse backgrounds. The aim was to investigate whether heterozygous loss of Smad4 increases susceptibility to spontaneous liver tumor development in a genetically diverse murine population. We generated 260 F1(C57BL/6J/Smad4^+/- X CC) mice, including 131 females and 129 males, by crossing Smad4^+/- males (C57BL/6J background) with females from 14 Collaborative Cross (CC) lines. Mice were maintained and monitored under standardized conditions for up to 80 weeks. Liver tissues were analyzed by gross pathology and histology for evidence of neoplasia. Tumor incidence was calculated per CC line; and Fisher's exact tests were used to evaluate line-specific susceptibility. Liver tumors developed in Smad4^+/- mice (8/260; 3.08%) background, with no tumors observed in wild-type littermates. Four CC lines exhibited tumor-positive, with elevated incidence in CC025 (15.79%, p = 0.0011), CC010 (8.33%, p = 0.0173), and CC005 (6.90%, p = 0.0241). After Bonferroni correction for multiple comparisons, only CC025 remained statistically significant. Histopathology confirmed hepatocellular carcinoma in representative cases. Tumor incidence showed no sex bias and was restricted to specific genotypic contexts, indicating an interaction between heterozygous Smad4 deletion and host genetic background. Partial loss of Smad4 promotes liver carcinogenesis in a strain-dependent manner, highlighting the importance of genetic modifiers in tumor susceptibility. The use of CC mice provides a valuable platform for uncovering genotype-specific cancer susceptibilities in preclinical research.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042723","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":"Chrysin attenuates diabetes-induced retinal injury by inhibiting microglial GBP3/NLRP3/GSDMD-mediated pyroptosis.","authors":"Qun Liu, Song-Min Wang, Xuan Chen, Yi-Rao You, Chen-Jiao Guo, Chang-Qin Xie, Lu-Lu Wang, Qi Liu, Lan Zhang, Jun-Tao Yang","doi":"10.1002/ame2.70293","DOIUrl":"10.1002/ame2.70293","url":null,"abstract":"<p><strong>Background: </strong>This study was designed to investigate whether chrysin, a natural flavone, alleviates experimental diabetic retinal disease and to define a microglia-centered mechanism involving guanylate-binding protein 3 (GBP3) and NLR family pyrin domain containing 3 (NLRP3)-gasdermin D (GSDMD) pyroptosis signaling.</p><p><strong>Methods: </strong>Streptozotocin (STZ)-diabetic mice received vehicle or chrysin for 4 weeks, followed by assessment of fasting blood glucose, serum caspase-1 and interleukin-1β (IL-1β) levels, retinal histology, Evans blue leakage, and retinal immunofluorescence for glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA-1), with apoptosis measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). In vitro, BV2 microglia were exposed to high glucose with vehicle or chrysin. Cell viability (Cell Counting Kit-8), oxidative stress (reactive oxygen species and malondialdehyde), and pyroptosis-associated markers were analyzed by Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence. RNA sequencing (RNA-seq) profiled transcriptional responses, and small interfering RNA (siRNA) was used to knock down GBP3.</p><p><strong>Results: </strong>In STZ-diabetic mice, chrysin reduced fasting glucose and circulating caspase-1 and IL-1β, partially preserved retinal thickness, and decreased vascular leakage. Chrysin attenuated GFAP upregulation, reduced IBA-1 signals, and lowered TUNEL-positive cells. In BV2 cells, chrysin improved viability, reduced oxidative stress, and suppressed NLRP3-GSDMD activation. RNA-seq highlighted chrysin-responsive pyroptosis signatures and identified GBP3 as a regulated node. GBP3 knockdown reduced high-glucose-associated NLRP3 and Gsdmd expression and diminished GSDMD cleavage.</p><p><strong>Conclusions: </strong>Chrysin protects the diabetic retina and suppresses microglial pyroptosis via a GBP3-linked NLRP3-GSDMD axis.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032276","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 stroke models and outcome evaluation: A review.","authors":"Solsa Cariba, Helen M Atkinson, Anthony K C Chan","doi":"10.1002/ame2.70289","DOIUrl":"10.1002/ame2.70289","url":null,"abstract":"<p><p>Stroke is among the leading causes of death and disability worldwide, and despite extensive research, prevalence is increasing. This has been partly attributed to systemic flaws in experimental design principles in studies involving stroke, and much work has been done to improve the standards of study design. In this article, different animal models mimicking ischemic and hemorrhagic stroke will be reviewed. Historical models will be discussed, as well as the more commonly employed modern techniques, such as thromboembolic occlusion and intraluminal filament occlusion models. This will be followed by a discussion of the selection of species for experimental animals, including the pros and cons of each. The various criteria used as metrics for evaluating post-stroke outcomes will also be reviewed, including but not limited to sensorimotor and cognitive impairment. Techniques for the evaluation of molecular, cellular, and hematological phenotypes will also be reviewed, including but not limited to in vitro and ex vivo cell culture, co-culture, and RNA/protein expression assays. Finally, a selection of key criteria and factors which have been historically neglected will be discussed, such as age and sex.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019004","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":"Association of DPP4 with esophageal stricture progression and the Hippo-YAP pathway.","authors":"Rui Wu, Chen Wang, Hui-Min Tao, Jin Huang, Wei-Qin Li, Zhi-Ning Fan","doi":"10.1002/ame2.70239","DOIUrl":"10.1002/ame2.70239","url":null,"abstract":"<p><strong>Background: </strong>Esophageal stricture (ES), a common complication after endoscopic submucosal dissection (ESD), is the consequence of excessive fibrosis and scar formation. The fibroblast-to-myofibroblast differentiation is a key characteristic in the pathogenesis of ES, but the molecular basis remains poorly understood.</p><p><strong>Methods: </strong>According to the human transcriptome sequencing analysis, which utilized different expression gene analysis and weighted gene co-expression network analysis, the potential gene associated with ES was explored. Furthermore, we utilized the rat model of ES and the temporal progression of ES after drug treatment to elucidate the role of DPP4 in ES. Subsequently, we identified a significant association between DPP4 and the progression of ES. Finally, we validated our conclusions through experiments on Bama pigs.</p><p><strong>Results: </strong>DPP4 expression was consistently elevated in both human ES tissues and the rat ES model. Upon inhibition of DPP4, the proliferative activity of ES primary cells and the expression of fibrosis-related genes were markedly suppressed. In rats, treatment with a DPP4 inhibitor significantly alleviated ES, which was accompanied by a significant reduction in collagen content and downregulation of fibrosis-related targets. These effects were observed in conjunction with changes in the Hippo-YAP pathway, although the data primarily support a parallel association rather than a hierarchical regulatory relationship between DPP4 and this pathway.</p><p><strong>Conclusions: </strong>Our findings suggest that DPP4 may contribute to the remodeling of the regenerative microenvironment in ES, with its expression and function occurring in parallel with alterations in the Hippo-YAP pathway. Direct mechanistic evidence establishing a linear upstream-downstream relationship between DPP4 and Hippo-YAP signaling remains to be further elucidated.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868256","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":"Neuroprotection after transient middle cerebral artery occlusion in male rats using kojic acid nanostructured lipid carriers: A behavioral, biochemical, and histological study on hippocampal CA1 region.","authors":"Mobina Gheibi, Erfan Ghadirzadeh, Javid Tebyani, Seyedeh Mohadeseh Moyaedi, Khadijeh Khezri, Majid Saeedi, Ali Siahposht-Khachaki, Narges Karimi, Melika Pourhossein, Shiva Shadi, Sasan Shafiei, Atena Sharifi-Razavi","doi":"10.1002/ame2.70285","DOIUrl":"10.1002/ame2.70285","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke triggers neuroinflammation and oxidative stress, leading to neuronal damage. Kojic acid (KA) has exhibited neuroprotective properties in other neurological pathologies but suffers from poor bioavailability. This study investigated whether KA encapsulated in nanostructured lipid carriers (KA-NLC) exerts protective effects against cerebral ischemia.</p><p><strong>Methods: </strong>Eighty adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) or control procedures and allocated into 10 experimental groups (n = 8 per group): intact, sham, MCAO, vehicle, three free-KA solution groups (10, 20, and 40 mg/kg), and three KA-NLC groups (1, 2, and 4 mg/kg). Functional outcomes were assessed using neurological scoring and Rota-Rod, Morris water maze, and shuttle box tests. Brain water content, hippocampal histology, and cerebrospinal fluid cytokine levels (interleukin-10 [IL-10], tumor necrosis factor-α [TNF-α]) were also evaluated.</p><p><strong>Results: </strong>Treatment with low and medium doses of KA-NLC and medium and high doses of free KA significantly reduced brain edema and improved neurological scores, motor coordination, and memory performance compared to the MCAO group. These functional improvements were associated with a significant increase in anti-inflammatory IL-10 and a modulation of TNF-α. Histological examination confirmed neuroprotection, with KA-NLC preserving hippocampal CA1 neural integrity. The high dose of KA-NLC and the low dose of free KA however were ineffective.</p><p><strong>Conclusions: </strong>Nanoformulated KA confers significant neuroprotection against ischemic stroke by reducing edema, modulating inflammation, and preserving neuronal integrity, presenting a promising therapeutic strategy.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868182","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}