Journal of Neuroinflammation最新文献

{"title":"SGK1 inhibition supports neuroprotection in spinal cord injury by suppressing oxidative stress and AIM2 activation via FoxO1 mediated mitophagy.","authors":"Yige Chen, Yikang Wang, Nongtao Fang, Jiawei Xu, Yiwei Teng, Ke Wang, Longze Huang, Haifen Ni, Yongli Wang, Kailiang Zhou, Yan Lin, Yao Li","doi":"10.1186/s12974-026-03844-w","DOIUrl":"https://doi.org/10.1186/s12974-026-03844-w","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is accompanied by a significant microglia-associated inflammatory response that is associated with secondary tissue damage and poorer functional outcomes. Serum and glucocorticoid-regulated kinase 1 (SGK1) has been implicated in the regulation of cell survival and neuronal excitability in various diseases. However, the role and cell-specific mechanism of SGK1 in SCI remain to be elucidated. In this study, we observed that SGK1 was predominantly expressed in microglia located at the lesion margin during the early phase of SCI in a mouse contusion model. Inhibition of SGK1 by GSK650394 has been shown to promote neural repair while simultaneously suppressing neuroinflammation and mitochondrial oxidative stress. Mechanistically, the inhibition of SGK1 results in a reduction of FoxO1 phosphorylation and the promotion of nuclear import, consequently inducing microglial mitophagy and promoting mitochondrial homeostasis, leading to the suppression of absent in melanoma 2 (AIM2) related pyroptosis and the conversion of microglia into a neuroprotective M2 phenotype. In particular, AIM2 overexpression or deletion effectively interfered with the influence of SGK1-FoxO1 on the modulation of SCI. In conclusion, the present findings provide a potential therapeutic strategy for the treatment of SCI.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816255","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":"MSC-EVs attenuate subretinal fibrosis in choroidal neovascularization through miR-21-5p-mediated inhibition of EMT and MMT and suppression of inflammation.","authors":"Xiang-Ling Yuan, David Hughes, Xuexue Cui, Ruiqi Zhou, Jinyan Qi, Caijiao Yi, Jian Liu, Sarah McFetridge, Johnatas Dutra Silva, Hojjat Naderi-Meshkin, Anna D Krasnodembskaya, Heping Xu, Mei Chen","doi":"10.1186/s12974-026-03836-w","DOIUrl":"https://doi.org/10.1186/s12974-026-03836-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (nAMD). Sustained macular inflammation drives the initiation and progression of fibrosis by activating profibrotic cells and perpetuating tissue damage. This study investigated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in mitigating nAMD-associated subretinal fibrosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;MSC-EVs were prepared from human bone marrow-derived MSCs and characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western Blotting. Subretinal fibrosis was induced in C57BL/6J mice using the two-stage laser-induced model. MSC-EVs were injected either intravitreally (1 × 10&lt;sup&gt;8&lt;/sup&gt; particles/eye, single injection) or retro-orbitally (1 × 10&lt;sup&gt;8&lt;/sup&gt; particles, two injections four days apart) immediately after the second laser. Eyes were collected 10 days post-second laser for immunostaining of collagen-1 and CD31 or iso-lectin B4. In vitro, primary human RPE and ARPE-19 cells were treated with TGF-β2 (10 ng/mL) to induce epithelial-mesenchymal transition (EMT); peritoneal macrophages were treated with TGF-β1 (10 ng/mL) to induce macrophage-to-myofibroblast transition (MMT). After 48 h, cells were treated with MSC-EVs (cell-to-MSC-EV ratio = 1:2000) for 3 days. Myofibroblast markers (αSMA, fibronectin, and collagen-1) were examined by immunocytochemistry and quantitative PCR (qPCR). Human iPCS-derived macrophages (iMACs), bone-marrow-derived macrophages, peritoneal macrophages, and BV2 microglia were treated with LPS (100 ng/mL) and IFN-γ (20 ng/mL) for 24 h with or without MSC-EVs (1:2000). Small RNA sequencing was used to identify specific functional molecules within MSC-EVs. Immune-related gene expressions were evaluated by qPCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Intravitreal and retroorbital administration of MSC-EVs reduced collagen-1&lt;sup&gt;+&lt;/sup&gt; fibrotic lesions by 46% and 30%, respectively, and significantly inhibited infiltrating Iba-1&lt;sup&gt;+&lt;/sup&gt; cells. In vitro, MSC-EVs attenuated TGF-β2-induced upregulation of αSMA, fibronectin, and collagen-1 at both protein and mRNA levels in RPE cells. Similarly, the expression of Acta2, Fn1, and Col1a1 in TGF-β1-treated macrophages was also significantly reduced following MSC-EV treatment. In LPS + IFN-γ-stimulated immune cells, MSC-EVs significantly suppressed the expression of Il6 and Il1b in all cell types, and reduced the expression of Inos, Tnfa, and Cd86 in iMACs, peritoneal macrophages, and BV2 cells. Enriched hsa-miR-21-5p was identified in MSC-EVs and involved in the TGF-β-related signaling pathway. Overexpression of miR-21-5p mimic abrogated the TGF-β1-driven upregulation of pro-fibrotic markers in RPE and macrophages.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Local administration of MSC-EVs effectively mitigated subretinal fibrosis and reduced inflammation in the mouse model of ","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816246","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":"PTP1B in astrocytes drives pathogen-induced neurodegeneration.","authors":"Zhicheng He, Yihui Xing, Jianqi Gu, Daxiang Xu, Peixuan He, Xiaoqian Lin, Wenjing Cui, Huiling Lv, Haoxuan Ding, Kai Sui, Wenting Hao, Yutao Zheng, Xiaoying Yang, Xufeng Huang, Kun Yin, Cheng He, Kuiyang Zheng, Yinghua Yu, Wei Pan","doi":"10.1186/s12974-026-03837-9","DOIUrl":"https://doi.org/10.1186/s12974-026-03837-9","url":null,"abstract":"<p><p>Mounting evidence implicates pathogen infections in the pathogenesis of Alzheimer's disease (AD), yet the cellular mechanisms underlying infection-induced neurodegeneration remain poorly understood. Central to this process is the dysfunction of astrocyte-neuron interactions, which are critical for maintaining neuroinflammatory balance and synaptic homeostasis. Here, we demonstrate that astrocytic protein tyrosine phosphatase 1B (PTP1B) acts as a key regulator of astrocyte reactivity during infection, leading to impaired neuroglial communications and cognitive decline. In a murine model of chronic Toxoplasma gondii (T. gondii) infection, elevated PTP1B levels in astrocytes were closely associated with neuroinflammation and cognitive impairments. Conditional deletion of astrocytic PTP1B or its pharmacological inhibition mitigated neuroinflammation, restored synaptic integrity, and rescued cognitive function. Mechanistically, astrocytic PTP1B induced the polarization of A1-like neurotoxic reactive astrocytes, enhanced glutamate-mediated excitotoxicity, and triggered neuronal senescence, collectively contributing to synaptic damage and cognitive deficits. Notably, elevated levels of PTP1B, GAFP and cellular senescence markers were observed in the serum samples from T. gondii IgG-seropositive individuals and in hippocampal transcriptomes from AD patients, underscoring the translational relevance. Together, our findings reveal that PTP1B-mediated disorder of astrocyte-neuron crosstalk represents a novel mechanism of pathogen-driven neurodegeneration.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774181","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":"Glioblastoma radiomics can delineate systemic immune activity states like blood abundance of T cell populations or transcription factors.","authors":"Johanna Heugenhauser, Carmen Visus, Johanna Buchroithner, Christine Marosi, Karl Rössler, Thomas Felzmann, Georg Widhalm, Sarah Iglseder, Martha Nowosielski, Friedrich Erhart","doi":"10.1186/s12974-026-03806-2","DOIUrl":"https://doi.org/10.1186/s12974-026-03806-2","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774245","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":"Short-chain fatty acids mitigate inflammation and associated metabolic programming of human stem cell-derived enteric glial cells.","authors":"Anastasia Markidi, Esther A Zaal, Lousanne H C de Wit, Maria Eleni Mavrogeni, Massimiliano Caiazzo, Aletta D Kraneveld, Paula Perez Pardo, Celia R Berkers","doi":"10.1186/s12974-026-03818-y","DOIUrl":"https://doi.org/10.1186/s12974-026-03818-y","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774186","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":"Lactate metabolism links reactive microglia, amyloid pathology, and Aβ dynamics.","authors":"Clair C Ashley, Nicholas J Constantino, Ryan J Pettit-Mee, J Andy Snipes, Kai Saito, Riley E Irmen, Rui Zhang, Evan M Neary, Matthew J Lanning, Celeste M Karch, Lance A Johnson, Josh M Morganti, Shannon L Macauley","doi":"10.1186/s12974-026-03825-z","DOIUrl":"https://doi.org/10.1186/s12974-026-03825-z","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774232","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":"Tryptophan-kynurenine metabolic reprogramming along the gut-brain axis alleviates Alzheimer's pathology.","authors":"Hyunjung Choi, Seok Beom Hong, Yumi Kim, Hyunchae Joung, Yukyung Choi, Jiah Cha, Ji Yong Park, Yun-Sang Lee, Hayoung Choi, Jong Won Han, Kyung Hwan Kim, Chang Hun Shin, Do Yup Lee, Inhee Mook-Jung","doi":"10.1186/s12974-026-03796-1","DOIUrl":"https://doi.org/10.1186/s12974-026-03796-1","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774339","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":"Neural impairments caused by energy storage material NCM811 via aberrated synaptic pruning: role of Th17 cells in microglia polarization.","authors":"Cuishuang Dong, Jiajing Cui, Yujie Bi, Nannan Huang, Bin Li, Xiaobo Li","doi":"10.1186/s12974-026-03831-1","DOIUrl":"https://doi.org/10.1186/s12974-026-03831-1","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774226","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":"Blood vessel-associated inflammatory microglia and astrocytes are associated with molecular and cellular markers of blood-brain barrier permeability in neonatal mice infected with the respiratory pathogen Bordetella pertussis.","authors":"Eoin O'Neill, Marina A Lynch, Kingston H G Mills","doi":"10.1186/s12974-026-03797-0","DOIUrl":"https://doi.org/10.1186/s12974-026-03797-0","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774200","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":"Glymphatic dysfunction contributes to thalamic iron retention and secondary thalamic injury after stroke: evidence from primates and rodents.","authors":"Jiating Wei, Xinran Chen, Qingfeng Lei, Jia Xie, Xiya Long, Zhiyi Xiong, Miaoxian Yang, Lisi Zha, Weixian Huang, Fubing Ouyang, Jinsheng Zeng","doi":"10.1186/s12974-026-03802-6","DOIUrl":"https://doi.org/10.1186/s12974-026-03802-6","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774212","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}