Journal of Neuropathology and Experimental Neurology最新文献_第8页

Mechanisms of fibrinogen trans-activation of the EGFR/Ca2+ signaling axis to regulate mitochondrial transport and energy transfer and inhibit axonal regeneration following cerebral ischemia. 纤维蛋白原转激活表皮生长因子受体/Ca2+信号轴调节线粒体转运和能量转移并抑制脑缺血后轴突再生的机制。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae114

Shengqiang Zhou, Bo Li, Dahua Wu, Yanjun Chen, Wen Zeng, Jia Huang, Lingjuan Tan, Guo Mao, Fang Liu

{"title":"Mechanisms of fibrinogen trans-activation of the EGFR/Ca2+ signaling axis to regulate mitochondrial transport and energy transfer and inhibit axonal regeneration following cerebral ischemia.","authors":"Shengqiang Zhou, Bo Li, Dahua Wu, Yanjun Chen, Wen Zeng, Jia Huang, Lingjuan Tan, Guo Mao, Fang Liu","doi":"10.1093/jnen/nlae114","DOIUrl":"10.1093/jnen/nlae114","url":null,"abstract":"Ischemic stroke results in inhibition of axonal regeneration but the roles of fibrinogen (Fg) in neuronal signaling and energy crises in experimental stroke are under-investigated. We explored the mechanism of Fg modulation of axonal regeneration and neuronal energy crisis after cerebral ischemia using a permanent middle cerebral artery occlusion (MCAO) rat model and primary cortical neurons under low glucose-low oxygen. Behavioral tests assessed neurological deficits; immunofluorescence, immunohistochemistry, and Western-blot analyzed Fg and protein levels. Fluo-3/AM fluorescence measured free Ca2+ and ATP levels were gauged via specific assays and F560nm/F510nm ratio calculations. Mito-Tracker Green labeled mitochondria and immunoprecipitation studied protein interactions. Our comprehensive study revealed that Fg inhibited axonal regeneration post-MCAO as indicated by reduced GAP43 expression along with elevated free Ca2+, both suggesting an energy crisis. Fg impeded mitochondrial function and mediated impairment through the EGFR/Ca2+ axis by trans-activating EGFR via integrin αvβ3 interaction. These results indicate that the binding of Fg with integrin αvβ3 leads to the trans-activation of the EGFR/Ca2+ signaling axis thereby disrupting mitochondrial energy transport and axonal regeneration and exacerbating the detrimental effects of ischemic neuronal injury.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"210-222"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576274","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

NOD-like receptor X1 promotes autophagy and inactivates NLR family pyrin domain containing 3 inflammasome signaling by binding autophagy-related gene 5 to alleviate cerebral ischemia/reperfusion-induced neuronal injury. nod样受体X1通过结合自噬相关基因5，促进自噬，灭活NLR家族pyrin结构域3炎性小体信号，减轻脑缺血再灌注诱导的神经元损伤。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae129

Yufen Peng, Yong Long, Chenyi Wan

{"title":"NOD-like receptor X1 promotes autophagy and inactivates NLR family pyrin domain containing 3 inflammasome signaling by binding autophagy-related gene 5 to alleviate cerebral ischemia/reperfusion-induced neuronal injury.","authors":"Yufen Peng, Yong Long, Chenyi Wan","doi":"10.1093/jnen/nlae129","DOIUrl":"10.1093/jnen/nlae129","url":null,"abstract":"Ischemic strokes pose serious risks to human health. We aimed to elucidate the function of NOD-like receptor X1 (NLRX1) in a rat middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injury (CIRI) model and in an oxygen-glucose deprivation/reperfusion (OGD/R)-treated human microglial cell line (HMC3) model. Following NLRX1 upregulation, infarct volumes were measured with 2,3,5-triphenyltetrazolium chloride staining and pathological examination was conducted with hematoxylin-eosin staining. Results suggested that levels of NLRX1 were decreased in brain tissue of MCAO rats and in OGD/R-stimulated HMC3 cells. NOD-like receptor X1 overexpression mitigated the neuronal damage, reduced tumor necrosis factor-α and interleukin-6 expression, alleviated microglial activation, and induced autophagy in vivo and in vitro. Additionally, a coimmunoprecipitation assay indicated that NLRX1 bound to autophagy-related gene 5 (ATG5) to elevate ATG5 expression in HMC3 cells. Further, the elevated NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, and cleaved caspase 1 expression in MCAO rats and HMC3 cells with OGD/R induction was reduced after NLRX1 upregulation. Importantly, ATG5 depletion abrogated the effects of NLRX1 elevation on NLRP3 inflammasome signaling. These results indicate that NLRX1 promotes autophagy and inactivates NLRP3 inflammasome signaling by binding ATG5 in experimental cerebral ischemia. These data may help the development of novel therapeutic strategies for ischemic stroke.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"223-235"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872382","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

Integrating molecular analyses with the 2021 WHO classification of adult pilocytic astrocytomas. 整合分子分析与2021年WHO成人毛细胞星形细胞瘤的分类。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae130

Beatriz Moreno-Torres, Irene Manzano-Benito, Diana Cantero, Ángel Romo, Ángel Rodríguez de Lope, Manuela Mollejo, Aurelio Hernández-Laín, Bárbara Meléndez

{"title":"Integrating molecular analyses with the 2021 WHO classification of adult pilocytic astrocytomas.","authors":"Beatriz Moreno-Torres, Irene Manzano-Benito, Diana Cantero, Ángel Romo, Ángel Rodríguez de Lope, Manuela Mollejo, Aurelio Hernández-Laín, Bárbara Meléndez","doi":"10.1093/jnen/nlae130","DOIUrl":"10.1093/jnen/nlae130","url":null,"abstract":"Pilocytic astrocytomas (PAs) are benign grade 1 gliomas according to the World Health Organization (WHO). They are common in children but rare in adults in whom they may have a worse prognosis. Pediatric PAs are usually associated with dysregulation of the mitogen-activated protein kinase (MAPK) pathway, often involving BRAF alterations such as the KIAA1549::BRAF (K-B) fusion or V600E mutation. We investigated the molecular characteristics of adult PA using gene-targeted next-generation sequencing and specific gene tests, including for K-B fusion, TERT promoter, and FGFR1 hotspot mutations. The most frequent molecular alterations detected involved the MAPK pathway, particularly affecting BRAF and NF1 genes (55%). The prevalence of the K-B fusion (>40%) was higher than previously reported, likely due to challenges in detecting it. We identified molecular alterations in some cases that raised the differential diagnosis of other tumor types, revealing limitations in the 2021 WHO classification for adult PA. After removing other diagnostic types that may mimic PA histology, no adult patients with a diagnosis of PA and K-B fusion died after more than 10 years of mean follow-up. These findings suggest that, similar to pediatric cases, PA in adults may be driven by a single molecular hit, where the K-B fusion is not related to poor outcome.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"255-263"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882289","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

Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset. 在国家阿尔茨海默氏症协调中心数据集中，揭示具有孤立和混合神经退行性过程的受试者的临床病理相关性。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-21 DOI: 10.1093/jnen/nlae134

Satomi Hiya, Carolina Maldonado-Díaz, Susan K Rohde, Mitzi M Gonzales, Leyla Canbeldek, Lakshmi S Kulumani Mahadevan, Raquel T Yokoda, A Campbell Sullivan, Alicia S Parker, Charles L White, Elena V Daoud, Victoria Flores-Almazan, John F Crary, Kurt Farrell, Jamie M Walker, Timothy E Richardson

{"title":"Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset.","authors":"Satomi Hiya, Carolina Maldonado-Díaz, Susan K Rohde, Mitzi M Gonzales, Leyla Canbeldek, Lakshmi S Kulumani Mahadevan, Raquel T Yokoda, A Campbell Sullivan, Alicia S Parker, Charles L White, Elena V Daoud, Victoria Flores-Almazan, John F Crary, Kurt Farrell, Jamie M Walker, Timothy E Richardson","doi":"10.1093/jnen/nlae134","DOIUrl":"10.1093/jnen/nlae134","url":null,"abstract":"Although Alzheimer disease neuropathologic change (ADNC) is the most common pathology underlying clinical dementia, the presence of multiple comorbid neuropathologies is increasingly being recognized as a major contributor to the worldwide dementia burden. We analyzed 1051 subjects with specific combinations of isolated and mixed pathologies and conducted multivariate logistic regression analysis on a cohort of 4624 cases with mixed pathologies to systematically explore the independent cognitive contributions of each pathology. Alzheimer disease neuropathologic change and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were both associated with a primary clinical diagnosis of Alzheimer disease (AD) and were characterized by an amnestic dementia phenotype, while only ADNC associated with logopenic variant primary progressive aphasia (PPA). In subjects with ADNC and comorbid LATE-NC, Lewy body disease, and/or cerebrovascular disease, the clinical phenotype was usually diagnosed during life as \"Probable AD.\" Conversely, the combination of ADNC with frontotemporal lobar degeneration with TDP-43, progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) resulted in a mixed clinical picture, with variable features of amnestic dementia, PPA subtypes, behavioral variant FTD, PSP syndrome, and CBD syndrome. These findings elucidate the cumulative effects of mixed pathologies and provide insights into interactions between neurodegenerative pathologies contributing to a variety of clinical dementia presentations.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"177-194"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895606","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

Comorbidities in early-onset sporadic versus presenilin-1 mutation-associated Alzheimer disease dementia: Evidence for dependency on Alzheimer disease neuropathological changes. 早发散发性与早老素-1突变相关的阿尔茨海默病痴呆的合并症：阿尔茨海默病神经病理改变依赖性的证据

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae122

Diego Sepulveda-Falla, Carlos Andrés Villegas Lanau, Charles White Iii, Geidy E Serrano, Juliana Acosta-Uribe, Barbara Mejía-Cupajita, Nelson David Villalba-Moreno, Pinzhang Lu, Markus Glatzel, Julia K Kofler, Bernardino Ghetti, Matthew P Frosch, Francisco Lopera Restrepo, Kenneth S Kosik, Thomas G Beach

{"title":"Comorbidities in early-onset sporadic versus presenilin-1 mutation-associated Alzheimer disease dementia: Evidence for dependency on Alzheimer disease neuropathological changes.","authors":"Diego Sepulveda-Falla, Carlos Andrés Villegas Lanau, Charles White Iii, Geidy E Serrano, Juliana Acosta-Uribe, Barbara Mejía-Cupajita, Nelson David Villalba-Moreno, Pinzhang Lu, Markus Glatzel, Julia K Kofler, Bernardino Ghetti, Matthew P Frosch, Francisco Lopera Restrepo, Kenneth S Kosik, Thomas G Beach","doi":"10.1093/jnen/nlae122","DOIUrl":"10.1093/jnen/nlae122","url":null,"abstract":"Studying comorbidities in early onset Alzheimer disease (AD) may provide an advantageous perspective on their pathogenesis because aging factors may be largely inoperative for these subjects. We compared AD comorbidities between early-onset sporadic cases and American and Colombian cases with PSEN1 mutations. AD neuropathological changes (ADNC) were very severe in all groups but more severe in the PSEN1 groups. Lewy body disease and cerebral white matter rarefaction were the most common (up to 60%) of AD comorbidities, followed by arteriolosclerosis (up to 37%), and large-vessel atherosclerosis (up to 20%). Differences between the 3 groups included earlier age of onset in the American PSEN1 cases, shorter disease duration in sporadic cases, and more frequent large-vessel atherosclerosis and cerebral amyloid angiopathy in the Colombian PSEN1 cases. Logistic regression models adjusted for age and sex found the presence of a PSEN1 mutation, an apolipoprotein ε4 allele and TDP-43 pathology to predict an earlier age of onset; Hispanic ethnicity and multiracial subjects were predictive of severe CAA. Comorbidities are common in early onset AD and should be considered when planning clinical trials with such subjects. However, they may be at least partially dependent on ADNC and thus potentially addressable by anti-amyloid or and/anti-tau therapies.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"104-113"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818453","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

Long survival in a patient with fumarate hydratase mutation-associated glioma. 富马酸氢化酶突变相关胶质瘤患者的长期存活。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae100

Regina R Reimann, Dorothee Gramatzki, Andrea Bink, Jürgen Hench, Stephan Frank, Martina Haberecker, Tibor Hortobagyi, Kristof Egervari, Doron Merkler, Kenneth Aldape, Michael Weller

引用次数: 0

Potential of the pharmacological inhibition of CCL2-CCR2 axis via targeting FROUNT to prevent the initiation and the progression of intracranial aneurysms in rats. 通过靶向 FROUNT 对 CCL2-CCR2 轴进行药理抑制以预防大鼠颅内动脉瘤的发生和发展的潜力。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae115

Isao Ono, Masahiko Itani, Akihiro Okada, Akitsugu Kawashima, Etsuko Toda, Yoshiki Arakawa, Yuya Terashima, Tomohiro Aoki

{"title":"Potential of the pharmacological inhibition of CCL2-CCR2 axis via targeting FROUNT to prevent the initiation and the progression of intracranial aneurysms in rats.","authors":"Isao Ono, Masahiko Itani, Akihiro Okada, Akitsugu Kawashima, Etsuko Toda, Yoshiki Arakawa, Yuya Terashima, Tomohiro Aoki","doi":"10.1093/jnen/nlae115","DOIUrl":"10.1093/jnen/nlae115","url":null,"abstract":"Intracranial aneurysms (IAs) affect 1%-5% of the public and are a major cause of subarachnoid hemorrhage. Currently, there is no medical treatment to prevent the progression or rupture of IAs. Recent studies have defined IA as a chronic inflammatory disease in which macrophages infiltrate intracranial arteries via the CCL2-CCR2 axis. The chemokine signal regulator FROUNT mediates this axis, and it can be inhibited by the anti-alcoholism drug disulfiram. Therefore, inhibition of macrophage infiltration by interfering with FROUNT using disulfiram may represent a strategy to prevent exacerbation of IAs. Here, effects of disulfiram were investigated in vitro and in an animal model of IAs. FROUNT expression was observed on infiltrated macrophages both in human IAs and in the rat IA model by immunohistochemistry. In vitro treatment with disulfiram suppressed CCL2-mediated migration of cultured rat macrophages in a transwell system. Disulfiram administered in a rat model of IAs inhibited both the initiation and the enlargement of IAs in a dose-dependent manner; this was accompanied by suppression of macrophage infiltration. These results suggest that pharmacological inhibition of the CCL2-CCR2-FROUNT signaling cascade could be a treatment of patients with IAs.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"132-140"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682047","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

Clinical and neuropathological analysis of Down syndrome over 7 decades of life. 唐氏综合征 70 年来的临床和神经病理学分析。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae110

Sonal Sukreet, Vanessa S Goodwill, Jennifer Ngolab, Ha Y Kim, Solana Leisher, Sahar Salehi, Michael S Rafii, Annie Hiniker, Robert A Rissman

引用次数: 0

Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization. 利用 16S rRNA 原位杂交技术检测脑脓肿中的革兰氏阳性和革兰氏阴性细菌。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae118

William Mbongo, Alvaro C Laga, Isaac H Solomon

{"title":"Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization.","authors":"William Mbongo, Alvaro C Laga, Isaac H Solomon","doi":"10.1093/jnen/nlae118","DOIUrl":"10.1093/jnen/nlae118","url":null,"abstract":"In situ hybridization (ISH) staining of bacterial 16S ribosomal RNA (rRNA) is an alternative to standard histological stains (eg, Gram, Warthin-Starry), and may improve the diagnosis of bacterial brain abscesses. To evaluate the utility of 16S rRNA ISH, a 10-year retrospective cohort was assembled from a large academic medical center. Results of histological stains, cultures, and 16S rRNA sequencing were extracted from reports, and new Gram and 16S rRNA ISH stains were performed. Histologically identifiable bacteria were present in 40/63 (63%) cases and 38/57 (67%) were associated with positive cultures. Overall, 16S rRNA ISH was positive in 18/63 (29%) cases, including 16/37 (43%) with positive Gram stains, 12/38 (32%) positive by culture, and 4/8 (50%) positive by sequencing. 16S rRNA ISH highlighted bacteria in 14/40 (35%) cases with Gram-positive organisms and 9/17 (53%) with Gram-negative organisms (including 6 polymicrobial cases). Compared to a composite gold standard of Gram stain and culture, the sensitivity and specificity of 16S rRNA ISH were 35% and 93%, respectively. While sensitivity is relatively low, 16S rRNA ISH may be useful for distinguishing real organisms from artifacts and for identifying brain abscess cases suitable for 16S rRNA sequencing.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"141-146"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605042","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

Tumor microtubes: A new potential therapeutic target for high-grade gliomas. 肿瘤微管：高级别胶质瘤的潜在治疗新靶点

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae119

Yunzhu Guo, Yangxin Li, Peng Su, Min Yan, Ming Wang, Shenjie Li, Wei Xiang, Ligang Chen, Wei Dong, Zhengjun Zhou, Jie Zhou

{"title":"Tumor microtubes: A new potential therapeutic target for high-grade gliomas.","authors":"Yunzhu Guo, Yangxin Li, Peng Su, Min Yan, Ming Wang, Shenjie Li, Wei Xiang, Ligang Chen, Wei Dong, Zhengjun Zhou, Jie Zhou","doi":"10.1093/jnen/nlae119","DOIUrl":"10.1093/jnen/nlae119","url":null,"abstract":"High-grade infiltrating gliomas are highly aggressive and fatal brain tumors that present significant challenges for research and treatment due to their complex microenvironment and tissue structure. Recent discovery of tumor microtubes (TMs) has provided new insights into how high-grade gliomas develop in the brain and resist treatment. TMs are unique, ultra-long, and highly functional membrane protrusions that form multicellular networks and play crucial roles in glioma invasiveness, drug resistance, recurrence, and heterogeneity. This review focuses on the different roles that TMs play in glioma cell communication, material transport, and tumor cell behavior. Specifically, non-connecting TMs primarily promote glioma invasiveness, likely related to their role in enhancing cell motility. On the other hand, interconnecting TMs form functional and communication networks by connecting with surrounding astrocytes and neurons, thereby promoting glioma malignancy. We summarize the factors that influence the formation of TMs in gliomas and current strategies targeting TMs. As the understanding of TMs advances, we are closer to uncovering whether they might be the long-sought Achilles' heel of treatment-resistant gliomas. By delving deeper into TMs research, we hope to develop more effective therapeutic strategies for patients with malignant gliomas.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"93-103"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668337","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