Burns & Trauma最新文献

{"title":"Neutrophils and NETs in Ischaemia–Reperfusion Injury: Pathophysiological Roles and Therapeutic Potential","authors":"Yiqiong Zhang, Chaofu Li, Qiuyan Jiang, Yukun Yang, Yingying Jiang, Lin Chen, Xiang Wei, Jun Xiao, Chuanwei Li","doi":"10.1093/burnst/tkag022","DOIUrl":"https://doi.org/10.1093/burnst/tkag022","url":null,"abstract":"Ischaemia–reperfusion injury (IRI) is a fundamental pathological process underlying acute and chronic damage associated with myocardial infarction, ischaemic stroke, and solid organ transplantation. Although timely reperfusion is indispensable for tissue salvage, it paradoxically promotes maladaptive immune activation and oxidative stress, which aggravate microvascular dysfunction and organ failure. Accumulating evidence indicates that sterile inflammation, endothelial injury, and immunothrombosis are the central drivers of IRI progression. Among innate immune effectors, neutrophils act as first responders that integrate chemotactic signalling, adhesion cascades, and metabolic rewiring. Upon activation, neutrophils release damage-associated molecular patterns (DAMPs) and form neutrophil extracellular traps (NETs), which amplify inflammation, promote coagulation, and disrupt tissue repair across organs. However, the organ-specific roles, temporal dynamics, and translational relevance of neutrophils and NETs in IRI remain incompletely understood. In this review, we systematically dissect the neutrophil- and NET-mediated mechanisms involved in IRI across the heart, brain, kidney, liver, and transplanted organs, with a particular emphasis on endothelial crosstalk, immunothrombosis, and metabolic regulation. We further summarize emerging NET-associated biomarkers—including cell-free DNA (cfDNA) and myeloperoxidase–DNA (MPO–DNA) complexes—for IRI diagnosis and prognosis. Finally, we evaluate therapeutic strategies targeting neutrophil recruitment, immune metabolism, and NET clearance, highlighting challenges for clinical translation. In summary, this review provides a mechanistic and translational framework for targeting neutrophils and NETs in precision therapies for IRI.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"18 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the c-Jun–Irf8–CD36 Axis Attenuates Fibrotic Scar Formation and Promotes Functional Recovery after Spinal Cord Injury","authors":"Min Feng, JiYu Li, Jieying Zhang, Hang Zhang, Wanhua Li, Yili Liu, Xiang Gao, Hanyue Yang, Zeyu Liu, Chong Gao, Ruiyang Xiao, Jianru Xiao, Xiaozhong Zhou, Leilei Gong, Songlin Zhou, Jian Zhao, Caiqi Cheng","doi":"10.1093/burnst/tkag020","DOIUrl":"https://doi.org/10.1093/burnst/tkag020","url":null,"abstract":"Background Fibrotic scar formation constitutes a significant pathological obstacle that impedes neural regeneration and long-term functional recovery following spinal cord injury (SCI). However, the spatial distribution of key pro-fibrotic mediators within lesion scars and the upstream regulatory mechanisms driving fibroblast activation remain inadequately defined. Methods This study integrated single-cell RNA sequencing and spatial transcriptomic profiling to characterize CD36 expression patterns and identify fibroblast subpopulations within SCI scars. Pharmacological interventions were administered in mouse SCI models, using salvianolic acid B (SAB) to inhibit CD36 and T5224 to block AP-1/c-Jun activity. Histological and immunofluorescence analyses were performed to assess fibroblast accumulation, extracellular matrix deposition, angiogenesis, and axonal regeneration, alongside longitudinal behavioral evaluations of locomotor function. Mechanistic validation of the regulatory pathway was achieved through CUT&Tag and dual-luciferase reporter assays to investigate c-Jun–Irf8–CD36 transcriptional regulation, complemented by integrated single-cell/spatial analyses to assess fibroblast subcluster remodeling post-treatment. Results Spatial and single-cell analyses demonstrated that CD36 is predominantly localized within lesion scars, correlating with fibrotic progression and preferentially upregulated in specific fibroblast subclusters. SAB-mediated CD36 inhibition markedly reduced P4HB+ fibroblast accumulation, alleviated fibrotic deposition, enhanced angiogenesis and axonal regeneration, and improved hindlimb functional recovery. Mechanistically, c-Jun was upregulated in scar regions and indirectly promoted CD36 transcription through Irf8 activation, establishing a c-Jun–Irf8–CD36 signaling axis. CUT&Tag and reporter assays confirmed c-Jun binding to the Irf8 promoter, leading to Irf8-driven CD36 transcription. Similarly, T5224 downregulated CD36 expression, reduced fibroblast aggregation and matrix deposition, facilitated vascular remodeling, and promoted early functional recovery. These findings demonstrate that modulating this signaling pathway can significantly inhibit pathological scar formation and facilitate approximately scar-free healing, thereby providing an ideal microenvironment for tissue regeneration. Multi-omic analyses further revealed that T5224 selectively inhibited the aberrant expansion of CD36+ fibroblast subclusters and reprogrammed their transcriptional states toward a less fibrotic phenotype. Conclusions The c-Jun–Irf8–CD36 axis serves as a pivotal regulator of fibrotic scar formation after SCI. Targeting this pathway through CD36 inhibition (SAB) or AP-1/c-Jun blockade (T5224) attenuates fibrosis, remodels the scar microenvironment, enhances tissue repair, and promotes functional recovery, highlighting a promising therapeutic strategy for central nervous system injury.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"5 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrion-targeted therapies for diabetic wound healing: from mechanism to therapeutic opportunity","authors":"Qipeng Wu, Fei Xiao, Han Wang, Yuan Xiong, Bobin Mi","doi":"10.1093/burnst/tkag018","DOIUrl":"https://doi.org/10.1093/burnst/tkag018","url":null,"abstract":"Diabetic wounds are a major clinical challenge. They are driven by persistent hyperglycemia and chronic inflammation that synergistically disrupt mitochondrial homeostasis, manifesting as impaired bioenergetics, excessive reactive oxygen species (ROS) accumulation, and dysregulated mitochondrial quality control. Mitochondrial dysfunction critically undermines cellular proliferation, angiogenesis, and immunomodulation, which are essential for effective tissue repair. Intercellular mitochondrial transfer, mediated through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junctions (GJs) and cell fusion, has recently emerged as a biologically compelling endogenous rescue mechanism capable of restoring bioenergetic capacity and redox homeostasis in metabolically compromised recipient cells. In this review, we systematically examine the mechanistic basis of mitochondrial dysfunction in the diabetic wound microenvironment, critically evaluate the therapeutic potential of intercellular mitochondrial transfer, and propose an integrated mechanism-to-translational framework coupling transfer-based strategies with bioresponsive and mitochondrion-targeted biomaterials tailored to the pathological wound milieu. Furthermore, we identify key translational barriers—including insufficient protocol standardization, the absence of robust characterization criteria, and a lack of quantitative benchmarks for transfer efficacy—that must be addressed to advance these strategies toward clinical application, thereby offering a conceptual foundation and translational roadmap for mitochondrion-centered regenerative approaches in diabetic wound care.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"32 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Research on Predicting Skin Flaps Necrosis through Quantification of the USP4/TNFAIP2 Regulated “M1 Macrophages-Tregs Axis” via Skin Barrier Monitoring Technology","authors":"Xuanlong Zhang, Xiaoqiong Jiang, Shenjie Song, Kaiyi Du, Hongxin Wang, Zihan Zhang, Yu Wang, Xiangwei Ling, Qingfeng Li","doi":"10.1093/burnst/tkag016","DOIUrl":"https://doi.org/10.1093/burnst/tkag016","url":null,"abstract":"Background Current methods used for assessing random-pattern skin flaps (RPSFs) viability are invasive and subjective. Therefore, developing an more accurate and non-invasive strategy for predicting RPSFs prognosis is important. This study discovered that skin barrier monitoring technology could predict RPSFs necrosis. In addition, the underlying mechanism was also clarified in this study. Methods Gene ontology (GO) analysis was employed to identify the potential pathways associated with RPSFs necrosis. Skin barrier monitoring technology, immunohistochemistry (IHC), immunofluorescence (IF) and western blotting (WB) were employed to assess skin barrier integrity, quantify ferroptosis level, and evaluate the recruitment of M1 macrophages and regulatory T cells (Tregs). Clinical samples were also included to validate the accuracy and efficacy of skin barrier monitoring technology in predicting RPSFs necrosis. Results The necrotic process in RPSFs was characterized by increased infiltration of M1 macrophages and Tregs, accompanied by activated ferroptosis and dysfunction of skin barrier. Notably, Tregs infiltration significantly reduced the necrotic area and restored skin barrier integrity of RPSFs by inhibiting ferroptosis and polarization of M1 macrophages. Mechanistically, USP4 regulated the interaction of M1 macrophages and Tregs (M1 macrophages-Tregs axis) via stabilization of TNFAIP2. Analysis of clinical samples revealed that skin barrier monitoring technology could serve as predictive strategy for RPSFs necrosis. Conclusion This study demonstrated that the USP4/TNFAIP2 pathway would regulate skin barrier function and ferroptosis via “M1 macrophages-Tregs axis” in RPSFs. And the skin barrier monitoring technology could serve as reliable method for RPSFs necrosis prediction.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"68 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147292666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal Decoding of Skin Biology: Development, Aging, Disease, and Regeneration","authors":"Xinran Ding, Runzhi Huang, Yixu Li, Zhaofan Xia, Shizhao Ji","doi":"10.1093/burnst/tkag019","DOIUrl":"https://doi.org/10.1093/burnst/tkag019","url":null,"abstract":"Skin shows distinct temporal dynamics and spatial heterogeneity during development, aging, disease, and regeneration. Although single-cell sequencing has revealed cellular diversity, its lack of spatial context limits the ability to characterize cells within their native tissue microenvironment. Factors such as acute injury and chronic wounds spatiotemporally disrupt skin homeostasis and induce complex remodeling and functional changes. Understanding these dynamic processes with spatiotemporal resolution remains a challenge in skin biology. Recent advances in spatiotemporal omics make it possible to integrate single-cell sequencing, spatial omics, and time series analyses, allowing the preservation of in situ cellular positions and revealing gene expression dynamics and intercellular networks. These technologies have reshaped the understanding of skin development and wound healing and have promoted advances in precision medicine and regenerative therapies. In this review, the applications of, recent advances in, and clinical translation potential of spatiotemporal omics in skin research are summarized. The construction of a high-resolution, spatiotemporal cellular atlas across the human skin life cycle will help identify key biomarkers, optimize regenerative strategies, and support personalized therapies.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"113 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147314855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organoid research: new concepts and new technologies","authors":"Jin Zhang, Yuezhou Wu, Tianzhuo Shen, Yingrui Mao, Hongjing Dou, Yi Lin, Zhen Geng, Zhanghua Li, Jiacan Su","doi":"10.1093/burnst/tkag015","DOIUrl":"https://doi.org/10.1093/burnst/tkag015","url":null,"abstract":"As three-dimensional biomimetic systems developed from stem cells or somatic cells, organoids have gradually evolved into important links between basic research and clinical application. Compared with traditional two-dimensional culture and animal models, organoids can better reflect the structure and function of tissues and organs in terms of physiological relevance and prediction efficiency. This review explores the integration of organoid technology with microfluidic technology, gene editing, and artificial intelligence, focusing on the prospects of these technologies for application in precision medicine, disease modelling, drug screening, and toxicology. In addition, the latest progress in organoid research, including organ-on-a-chip, organoid biobank construction, and related applications of regenerative medicine, is summarized. The development of key technologies is reviewed in detail. These technologies include improvements in culture systems, innovations in microfluidic and matrix materials, gene editing and modification, and imaging and multiomic analyses. These achievements improve the application value of organoids in disease modelling, drug screening and toxicology. Despite challenges such as standardization, batch-to-batch consistency, and clinical translation, the integration of interdisciplinary technologies has provided a new impetus for the development of organoids. In the future, the combination of organoids with artificial intelligence, personalized medicine and regenerative medicine is expected to drive research progress on disease mechanisms and precision treatment.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"35 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146205099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption.","authors":"","doi":"10.1093/burnst/tkag014","DOIUrl":"https://doi.org/10.1093/burnst/tkag014","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/burnst/tkad054.].</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 ","pages":"tkag014"},"PeriodicalIF":9.6,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking the vicious cycle of impaired angiogenesis and chronic inflammation in diabetic wounds: a bioengineered microneedle system delivering RGD-modified M2 exosomes.","authors":"HongYu Wang, BaoHua Wei, BaiShi Wang, Mi Chai, Jing Ren, Yan Han, LingLi Guo","doi":"10.1093/burnst/tkag013","DOIUrl":"10.1093/burnst/tkag013","url":null,"abstract":"<p><strong>Background: </strong>Persistent local tissue hypoperfusion and chronic inflammation are central challenges in diabetic wound management. The development of effective therapeutic strategies to mitigate prolonged inflammation and enhance tissue vascularization is crucial for accelerating diabetic wound healing. This study aimed to develop soluble microneedle materials that simultaneously target both aspects to improve the clinical prognosis of diabetic wounds.</p><p><strong>Methods: </strong>A stable macrophage cell line overexpressing basic fibroblast growth factor (bFGF) was established using lentiviral transfection. After M2 polarization was induced with interleukin-4 (IL-4) and IL-10, exosomes were isolated via ultracentrifugation and surface-functionalized with arginine-glycine-aspartic acid (RGD)-targeting peptides. The reparative effects of these exosomes on human umbilical vein endothelial cells (HUVECs) with high glucose-induced injury were evaluated using scratch test, 5-ethynyl-2'-deoxyuridine (EdU) staining, and cell counting kit-8 assays. A delivery system based on soluble hyaluronic acid microneedles (MNs) loaded with engineered exosomes was then developed. Its therapeutic efficacy was evaluated in a diabetic wound mouse model, and the underlying mechanisms were explored via ribonucleic acid (RNA) sequencing.</p><p><strong>Results: </strong>Targeted engineered exosomes (TE-Exos) derived from bFGF-overexpressing M2 macrophages with surface RGD modification were successfully prepared. Assays revealed that TE-Exos exhibited specific targeting to HUVECs with high glucose-induced injury and significantly enhanced cellular proliferation, migration, and tube formation. Furthermore, the polarization ratio of macrophages improved after TE-Exos treatment. <i>In vivo</i>, the MN-mediated delivery of TE-Exos markedly accelerated diabetic wound healing by enhancing re-epithelialization, collagen deposition, and angiogenesis. Furthermore, the treatment modulated the wound microenvironment by reducing the infiltration of proinflammatory M1 macrophages while increasing the proportion of reparative M2 macrophages. RNA sequencing analysis indicated that the therapeutic effects were mediated primarily through the inhibition of excessive inflammation and the activation of angiogenesis-related signaling pathways.</p><p><strong>Conclusions: </strong>This innovative strategy breaks the vicious cycle of impaired angiogenesis and chronic inflammation in diabetic wounds through a synergistic mechanism involving 'angiogenesis, inflammation regulation, and precise delivery'. The combination of targeted exosome engineering with an MN delivery system not only overcomes the limitations of conventional growth factor therapies but also enables intelligent modulation of the wound microenvironment, offering novel theoretical insights and practical approaches for clinical translation.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 ","pages":"tkag013"},"PeriodicalIF":11.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin promotes skin flap survival by inhibiting ferroptosis","authors":"Mi Liu, Jiacheng Hu, Jiayi Huang, Zhefeng Cai, Peng Zou, Jing Bu, Shanshan Yu, Yuxi Zhou, Xiaoqiong Jiang, Lianfang Gan, Shuhong Tian, Lei Dong, Fenzan Wu, Huiming Deng, Jian Xiao","doi":"10.1093/burnst/tkag012","DOIUrl":"https://doi.org/10.1093/burnst/tkag012","url":null,"abstract":"Background Random skin flaps application is considerably limited by postoperative complications, particularly distal tissue ischemia and necrosis. Melatonin, a molecule with well-documented antioxidant and cytoprotective properties, has shown promise in protecting ischemic tissues. However, its specific role in regulating ferroptosis during ischemic flap injury, as well as its safety and efficacy in primate models (a key step for clinical translation), remains to be systematically validated. In this study, we aimed to promote angiogenesis within flap tissue through exogenous melatonin administration, and to inhibit ferroptosis to mitigate ischemia-reperfusion injury, presenting a novel strategy for enhancing flap survival rates. Methods A random skin flap was constructed in C57BL/6J mice. After melatonin treatment for seven days, the influence of melatonin on the levels of oxidative stress, iron accumulation, and mitochondrial morphology within the skin flap tissue were assessed. We used Transwell migration assays, tube formation assays, flow cytometry and immunofluorescence staining to determine the effects of melatonin in vitro. The ferroptosis inducer erastin was used in combination with melatonin to treat random skin flap mice and Tert-butyl hydroperoxide (TBHP) induced cellular models, And the pathway through which melatonin counteracts iron mutations was explored. Lastly, we conducted experiments using nonhuman primate (NHP) models and analyzed the protective effects of melatonin on ischemic flaps in macaques, highlighting its potential for clinical translation. Results Melatonin ameliorated the survival area of ischemic flaps in mice, enhanced angiogenesis, reduced mitochondrial damage, and also suppressed lipid peroxidation and iron ion accumulation. Melatonin attenuated TBPH-induced cell death, lipid peroxidation, and mitochondrial damage in vitro. Further mechanistic studies revealed that melatonin inhibited ferroptosis, accompanied by nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), and increases the expression of downstream gene (effector) heme oxygenase-1 (HO-1). More importantly, experiments in macaques demonstrated that melatonin could enhance flap viability and angiogenesis, and exhibited good safety profile. Conclusion Melatonin enhanced flap viability in mice and macaques by inhibiting ferroptosis, boosting angiogenesis, and attenuating oxidative stress injury.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"41 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mitofusin 1-mediated mitochondrial dynamics to suppress neuroinflammation and pyroptosis after traumatic brain injury.","authors":"Tao Liu, Liang Mi, Bo Chen, Meng Nie, Shuo Wang, Bo Wang, Yunhu Yu, Rongcai Jiang","doi":"10.1093/burnst/tkag011","DOIUrl":"10.1093/burnst/tkag011","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) can cause neuroinflammation and neuronal death. The role of mitochondrial dysfunction in regulating inflammasome activation during TBI remains unclear. This study aims to explore mitochondrial regulation of neuroinflammation and pyroptosis after TBI.</p><p><strong>Methods: </strong>We used a mouse TBI model and <i>in vitro</i> scratch-injured HT22 cells and primary neurons to examine changes in mitochondrial dynamics and nucleotide-binding oligomerization domain-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome activation. Metformin treatment, mitofusin 1 (Mfn1) knockdown and regulation of the Mfn1 pathway were applied to evaluate the therapeutic effects and mechanisms.</p><p><strong>Results: </strong>TBI triggered NLRP3 inflammasome activation and neuronal pyroptosis, along with impaired mitochondrial function and oxidative stress. Metformin reduced inflammasome activation, improved mitochondrial homeostasis, and alleviated neuronal injury. These effects were lost when Mfn1 was silenced, highlighting its essential role. Furthermore, we determined that the AMPK pathway modulates these observed effects.</p><p><strong>Conclusion: </strong>Metformin protects against TBI-induced neuronal damage by restoring Mfn1-dependent mitochondrial dynamics and suppressing inflammasome activation. Mfn1 is a key mediator linking mitochondrial health to neuroinflammatory responses in TBI.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 ","pages":"tkag011"},"PeriodicalIF":11.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}