Journal of Neuropathology and Experimental Neurology最新文献_第6页

YAP1::MAML2 fusion-positive high-grade neuroepithelial tumors with rhabdoid morphology and inflammatory microenvironment: Implications for integrated diagnosis. YAP1::MAML2融合阳性高级别神经上皮肿瘤伴横纹肌样形态和炎症微环境：对综合诊断的意义

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-26 DOI: 10.1093/jnen/nlag069

Hainan Li, Xuemin Wei, Tiantian Han, Wenting Li, Chongzhu Fan, Rongrong Kong, Xing Zhang, Dongsheng Chen, Yuhong Meng, Zhi Li

{"title":"YAP1::MAML2 fusion-positive high-grade neuroepithelial tumors with rhabdoid morphology and inflammatory microenvironment: Implications for integrated diagnosis.","authors":"Hainan Li, Xuemin Wei, Tiantian Han, Wenting Li, Chongzhu Fan, Rongrong Kong, Xing Zhang, Dongsheng Chen, Yuhong Meng, Zhi Li","doi":"10.1093/jnen/nlag069","DOIUrl":"https://doi.org/10.1093/jnen/nlag069","url":null,"abstract":"YAP1 fusions are well documented in pediatric central nervous system (CNS) tumors, particularly in supratentorial ependymomas and meningiomas where they are generally associated with a favorable prognosis. Outside these entities, YAP1 fusions have rarely been reported in gliomas or other high-grade neuroepithelial tumors. Here, we describe 2 high-grade neuroepithelial tumors harboring a recurrent YAP1::MAML2 fusion. Comprehensive histopathologic evaluation, immunohistochemistry, whole-exome sequencing using the SimcereDx neuro-oncology panel, and DNA methylation profiling were performed. Both tumors were IDH- and H3-wildtype and lacked canonical alterations in the RTK, TP53, or MAPK pathways. DNA methylation profiling did not match any established CNS tumor class. Histologically, both tumors demonstrated rhabdoid morphology accompanied by a prominent inflammatory microenvironment enriched in CD68- and CD163-positive macrophages. Despite sharing the same fusion event, the 2 tumors exhibited divergent morphologic and immunophenotypic features, indicating substantial heterogeneity. These findings suggest a potentially distinct, molecularly defined tumor subgroup characterized by YAP1::MAML2 fusion, high-grade neuroepithelial morphology, rhabdoid features, and an inflammatory microenvironment. They highlight the limitations of current methylation-based classification for such rare entities. Accurate diagnosis requires an integrated approach incorporating histologic features, clinical context, immunophenotype, and molecular alterations.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

+7/-10 chromosome copy-number alteration in the elderly: A cautionary tale from 2 cases. 老年人+7/-10染色体拷贝数改变：2例警示

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-24 DOI: 10.1093/jnen/nlag070

Ege Cubuk, Kenneth Aldape, Martha Quezado, Zied Abdullaev, Ganesh Rao, Akash J Patel, Jacob J Mandel, Zaid Ali Siddiqui, Hsiang-Chih Lu

引用次数: 0

Knockdown of TRIM21 inhibits ferroptosis via the p62-Keap1-Nrf2 pathway thereby improving brain injury and mitochondrial dysfunction after ischemia-reperfusion in mice. 敲低TRIM21可通过p62-Keap1-Nrf2途径抑制铁下沉，从而改善小鼠缺血再灌注后脑损伤和线粒体功能障碍。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-20 DOI: 10.1093/jnen/nlag075

Bo Yang, Yanxia Sun, Yao Zhang, Yanli Gu, Zheng Liu

{"title":"Knockdown of TRIM21 inhibits ferroptosis via the p62-Keap1-Nrf2 pathway thereby improving brain injury and mitochondrial dysfunction after ischemia-reperfusion in mice.","authors":"Bo Yang, Yanxia Sun, Yao Zhang, Yanli Gu, Zheng Liu","doi":"10.1093/jnen/nlag075","DOIUrl":"https://doi.org/10.1093/jnen/nlag075","url":null,"abstract":"Ferroptosis has a crucial role in cerebral ischemia-reperfusion injury (IRI) but its potential modulation is a key challenge in the treatment of ischemic stroke. The function and mechanism of the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21) in neurological diseases, particularly its regulatory role in ferroptosis are unclear. We used a mouse model of transient middle cerebral artery occlusion (tMCAO/R) and a PC12 cell model of oxygen-glucose deprivation/reperfusion (OGD/R) to investigate the effects of virus-mediated gene knockdown of TRIM21. Effects were assessed using Western blotting, immunoprecipitation, biochemical assays, and behavioral tests. TRIM21 expression was significantly increased after cerebral IRI. Knockdown of TRIM21 improved neurological deficits, reduced cerebral infarct size, and suppressed inflammation. Knockdown of TRIM21 also inhibited ferroptosis and improved mitochondrial function whereas TRIM21 negatively regulated the p62-Keap1-Nrf2 pathway through ubiquitination of p62. Salvage experiments confirmed that Nrf2 is a key downstream molecule for the neuroprotective effects of TRIM21. The data indicate that TRIM21 inhibition of the Keap1-Nrf2 pathway through p62 ubiquitination exacerbated ferroptosis after ischemic stroke in the tMCAO/R model and suggest that targeted inhibition of TRIM21 holds promise as a novel strategy for treating ischemic stroke.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A rare MYBL1-altered pediatric-type diffuse astrocytoma with positive OLIG2 and MAP2 expression and high proliferative activity. 罕见的mybl1改变的小儿型弥漫性星形细胞瘤，OLIG2和MAP2阳性表达，高增殖活性。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-18 DOI: 10.1093/jnen/nlag080

Min Zhou, Junjie Yang, Zejun Duan, Jing Feng, Zhong Ma, Zejuan Hu, Lei Xiang, Xueling Qi

引用次数: 0

Clinicopathologic characterization of a non-expansile, epilepsy-associated neocortical lesion with BRAF K601E mutation. BRAF K601E突变的非扩张性癫痫相关新皮质病变的临床病理特征

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-15 DOI: 10.1093/jnen/nlag055

Sangeetha Ramachandran, Ana E Berglind, Julien Hébert, Yewon Jung, Molly J Murch, Sandra Perez, Matthew Barkovich, Kanish Mirchia, Edward F Chang, Peter Canoll, Manu Hegde, Arie Perry, Melodie Winawer, Erin L Heinzen, Cathryn R Cadwell

引用次数: 0

Spinal high-grade astrocytoma with piloid features presenting with progressive encephalopathy, hypoglycorrhachia, hydrocephalus, and leptomeningeal dissemination. 脊柱高级别星形细胞瘤伴髓样特征，表现为进行性脑病、低糖下丘脑、脑积水和脑膜轻散。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-14 DOI: 10.1093/jnen/nlag076

Maximilian Mastall, Ramona-Alexandra Todea, Martin Zoche, Cäcilia Mader, Elena Luib, Francesco Capecchi, Corinne Inauen, Tibor Hortobágyi, Michael Weller

引用次数: 0

RagC and Map4K3 deficiency in high-grade gliomas drives proliferation and modulates mTORC1-dependent cellular functions. 高级别胶质瘤中RagC和Map4K3缺乏驱动增殖并调节mtorc1依赖的细胞功能。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-01 DOI: 10.1093/jnen/nlag010

Julian Kahr, Roberto Diaz-Peregrino, Ibrahim E Sandalcioglu, Peter John, Christian Mawrin

{"title":"RagC and Map4K3 deficiency in high-grade gliomas drives proliferation and modulates mTORC1-dependent cellular functions.","authors":"Julian Kahr, Roberto Diaz-Peregrino, Ibrahim E Sandalcioglu, Peter John, Christian Mawrin","doi":"10.1093/jnen/nlag010","DOIUrl":"10.1093/jnen/nlag010","url":null,"abstract":"Cellular growth and homeostasis via amino acid-responsive pathways are mediated by the mTOR signaling pathway. Rag GTPases and Map4K3 modify mTOR signaling as amino acid sensors. Altered mTOR signaling in relation to amino acid sensors might represent factors that modify proliferation and treatment responses in astrocytic tumors. To investigate this hypothesis, RagC and Map4K3 expression was studied in human gliomas, glioma cells (U87MG/U138MG), and nonglial cells (MCF-7, IOMM-Lee). RagC and Map4K3 knockout in glioma cells was generated using CRISPR-Cas and shRNA. High-grade astrocytomas had significantly reduced immunoreactivity for RagC and Map4K3 compared to low-grade astrocytomas. RagC- and Map4K3-deficient glioma cells had significantly increased proliferation and showed altered morphology and motility. Induced amino acid deficiency (leucine deprivation) reduced proliferation in Map4K3- but not in RagC-deficient cells. mTOR signaling in RagC- and Map4K3-deficient U87 cells was altered with increased phosphorylation of p70S6K and increased expression of RagD and transcription factor EB. In this context, uncoupled, exaggerated autophagy occurred in Map4K3-deficient U87 cells. In contrast, RagC-deficient U87 cells showed increased senescence but no autophagy induction. These data show that losses of RagC and Map4K3 in malignant gliomas have proliferation-inducing effects and differentially modulate key mTOR signaling-dependent cellular mechanisms.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"777-788"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Three-dimensional approaches to measuring primary cilia in hippocampal neurons: A comparative analysis. 三维测量海马神经元初级纤毛的方法：比较分析。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-01 DOI: 10.1093/jnen/nlag001

Sofia Rasmusson, Seyedeh Marziyeh Jabbari Shiadeh, Nour Dada, Ellen Åkesson, Carina Mallard, Maryam Ardalan

{"title":"Three-dimensional approaches to measuring primary cilia in hippocampal neurons: A comparative analysis.","authors":"Sofia Rasmusson, Seyedeh Marziyeh Jabbari Shiadeh, Nour Dada, Ellen Åkesson, Carina Mallard, Maryam Ardalan","doi":"10.1093/jnen/nlag001","DOIUrl":"10.1093/jnen/nlag001","url":null,"abstract":"Primary cilia are non-motile sensory organelles that detect extracellular signals; disruptions in their functions are linked to neurodevelopmental disorders. Because cilia lengths can rapidly change in response to stressors, they are important for both plasticity and brain homeostasis. Accurate measurement of ciliary length is therefore essential but the absence of standardized methods and the variability introduced by different techniques can compromise measurement reliability and precision. To address this challenge, our study employed two distinct methods to estimate the length of primary cilia in hippocampal subregions in mice. We compared stereology-based 3D quantification, which is considered a methodological gold standard due to its unbiased sampling design and correction for tissue shrinkage, with 3D reconstruction to measure primary cilia length. 3D reconstruction imaging used a 100× oil-immersion objective. With neuronal cilia typically ∼2-10 µm long in hippocampus, a 1-µm z-step provided multiple optical sections per cilium thereby ensuring full structural visualization. Our findings show that both methods allow simple and equally precise measurements of neuronal primary cilia length in hippocampal subregions. Their strong agreement provides researchers with reliable tools for studying primary cilia on immunohistochemically stained sections and supports a consistent methodological framework for investigating cilia dynamics.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"756-767"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gliomas with succinate dehydrogenase deficiency: A case series and brief review of the literature of oncometabolite-driven gliomagenesis. 琥珀酸脱氢酶缺乏的胶质瘤：肿瘤代谢物驱动的胶质瘤形成的病例系列和文献综述。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-01 DOI: 10.1093/jnen/nlag004

Madison T Gray, Romain Cayrol, Adriana May, John M Skaugen, Fadi Hayek, Sarah Lapointe, Cynthia E Hawkins, Thomas M Pearce, Drew Pratt, Danica Wiredja, Angus Toland, Daniel F Marker

{"title":"Gliomas with succinate dehydrogenase deficiency: A case series and brief review of the literature of oncometabolite-driven gliomagenesis.","authors":"Madison T Gray, Romain Cayrol, Adriana May, John M Skaugen, Fadi Hayek, Sarah Lapointe, Cynthia E Hawkins, Thomas M Pearce, Drew Pratt, Danica Wiredja, Angus Toland, Daniel F Marker","doi":"10.1093/jnen/nlag004","DOIUrl":"10.1093/jnen/nlag004","url":null,"abstract":"Oncometabolite production plays a key role in the development and progression of isocitrate dehydrogenase-mutant gliomas. The aberrant gain-of-function activity of the mutant isocitrate dehydrogenase protein results in the production of the oncometabolite D-2-hydroxyglutarate, which in turn promotes DNA hypermethylation and gliomagenesis through several mechanisms. Rare gliomas in patients with fumarate hydratase deficiency syndrome share many morphologic and molecular features with isocitrate dehydrogenase-mutant gliomas, with the oncometabolites succinate and 2-succinocysteine similarly thought to promote global DNA hypermethylation. Like isocitrate dehydrogenase and fumarate hydratase, succinate dehydrogenase is also a member of the citric acid cycle that additionally participates in oxidative phosphorylation. While succinate dehydrogenase deficiency has been implicated in familial tumor syndromes, it has not yet been associated with glial neoplasms. Here we report 3 cases of diffuse glioma with succinate dehydrogenase deficiency that show many similarities with isocitrate dehydrogenase-mutant gliomas. We propose that succinate dehydrogenase deficiency with accumulation of the oncometabolite succinate can promote gliomagenesis in a similar manner as seen in isocitrate dehydrogenase-mutant and fumarate hydratase-deficient gliomas, and we discuss the proposed mechanisms that may lead to tumor formation.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"789-796"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Azetidine-2-carboxylic acid-induced oligodendrogliopathy in vitro and the pathogenesis of multiple sclerosis. 氮杂啶-2-羧酸诱导的体外少突胶质病变及多发性硬化症的发病机制。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-01 DOI: 10.1093/jnen/nlag018

Raymond A Sobel, Julian R Hinojoza, Muhammad Zoabi

{"title":"Azetidine-2-carboxylic acid-induced oligodendrogliopathy in vitro and the pathogenesis of multiple sclerosis.","authors":"Raymond A Sobel, Julian R Hinojoza, Muhammad Zoabi","doi":"10.1093/jnen/nlag018","DOIUrl":"10.1093/jnen/nlag018","url":null,"abstract":"Azetidine 2-carboxylic acid (Aze) is consumed by humans and can be misincorporated in place of proline (Pro) in myelin basic protein (MBP). In systemically treated mice Aze induced distinct oligodendroglial (OL) alterations mimicking those in multiple sclerosis (MS) patient normal-appearing white matter. Here, Aze induced an unfolded protein response (UPR), cytoplasmic MBP aggregation, apoptosis and tumor necrosis factor secretion in the human OL lineage MO13.3 cell line. These alterations were counteracted by equimolar Pro suggesting that they are due to Aze substitution for Pro in OL proteins. Gene set enrichment analysis demonstrated extensive Aze-induced alterations of cell cycle, cytoskeletal, organelle, transport, developmental, inflammation-associated and myelination pathways that are altered in OL in MS patients and in toxin and inflammatory MS animal models. These data provide mechanistic support for the hypothesis that Aze protein misincorporation during early life myelinogenesis might over time result in a progressive UPR culminating in a pro-inflammatory/immunomodulatory phenotype, intracytoplasmic MBP aggregation, accelerated senescence and apoptosis in OL. This could occur prior to and independent of an external immune stimulus such as a viral infection. Aze-induced pathological alterations might enhance subsequent antiviral and autoimmune responses and contribute to MS susceptibility, lesion pathogenesis, remyelination failure, neurodegeneration and clinical progression.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"714-735"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0