Acta Neuropathologica Communications最新文献

{"title":"JMJD6-driven epigenetic activation of COL4A2 reprograms glioblastoma vascularization via integrin α1β1-dependent PI3K/MAPK signaling.","authors":"Yangyang Wu, Yanan Wu, Shuchou Xia, Hongkai Lian, Yongli Lou, Lin-Jian Wang","doi":"10.1186/s40478-025-02114-9","DOIUrl":"10.1186/s40478-025-02114-9","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM), the most aggressive primary brain malignancy in adults, is characterized by extensive vascularization and resistance to conventional anti-angiogenic therapies. In this study, through comprehensive integrative analyses of bulk RNA-seq and single-cell RNA-seq data, we identify COL4A2 as a critical orchestrator of vascularization in GBM. Elevated COL4A2 not only promotes epithelial-mesenchymal transition (EMT) in glioma cells, but also increases vascularization in GBM. Multi-omics profiling and mechanistic investigations reveal that aberrant expression of the anti-pause enhancer JMJD6 mediates the upregulation of COL4A2 in GBM. Furthermore, we demonstrate that COL4A2 promotes GBM vascularization by activating PI3K-AKT and MAPK-ERK signaling through interaction with ITGA1/ITGB1 receptors on tumor-associated endothelial cells (TECs). Pharmacological inhibition of the COL4A2-ITGA1/ITGB1 axis with obtustatin attenuates pro-angiogenic signaling, suppresses vascularization, and prolongs survival in orthotopic GBM models. Collectively, our findings establish JMJD6-driven COL4A2-ITGA1/ITGB1 axis as a novel anti-angiogenic therapeutic vulnerability, offering a promising strategy to disrupt TEC-tumor symbiosis and impede GBM progression.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"194"},"PeriodicalIF":5.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New experimental therapies for glioblastoma: a review of preclinical research.","authors":"Arseniy E Yuzhalin","doi":"10.1186/s40478-025-02105-w","DOIUrl":"10.1186/s40478-025-02105-w","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"199"},"PeriodicalIF":5.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning based semi-automated model can predict lineage in patients with pituitary neuroendocrine tumors.","authors":"Guoqing Wu, Zehang Ning, Xiaorong Yan, Jianfang Li, Chiyuan Ma, Haixia Cheng, Zixiang Cong, Junjun Li, Shengyu Sun, Yongfei Wang, Xingli Deng, Changzhen Jiang, Hong Chen, Hui Ma, Jinhua Yu, Nidan Qiao","doi":"10.1186/s40478-025-02104-x","DOIUrl":"10.1186/s40478-025-02104-x","url":null,"abstract":"<p><p>Pituitary neuroendocrine tumors (PitNETs) represent the most prevalent category of neuroendocrine neoplasms. Contemporary classification paradigms emphasize transcription factor immunohistochemistry (IHC) as a cornerstone for molecular subtyping and risk stratification. However, the clinical adoption of this approach is hindered by the lack of standardized interpretative thresholds for antibody staining and limited global availability of specialized reagents, particularly in resource-limited settings. To address these challenges, we developed a semi-automated computational framework that predicts PitNET lineages directly from hematoxylin and eosin (H&E)-stained histology slides. The pipeline employs a dynamic confidence threshold: samples below this threshold undergo confirmatory IHC staining and manual pathological review, while those surpassing it are classified automatically. In prospective validation, this approach achieved a 68.9% reduction in diagnostic workload while maintaining 95.9% overall accuracy. Similar efficacy was observed in functional (74.4% workload reduction, 99.0% accuracy) and external (39.3% reduction, 95.1% accuracy) cohorts. Statistical analysis confirmed non-inferiority between semi-automated predictions and fully manual IHC-based evaluations in all the cohorts. Furthermore, we implemented a deep learning-based virtual IHC staining module, generating synthetic transcription factor images demonstrating high morphological concordance with ground-truth IHC slides. Notably, our computational analysis revealed distinct histomorphological correlates of lineages: SF1-lineage tumors exhibited homogeneous cellular architecture characterized by densely packed, compact cells with reduced cytoplasmic volume, whereas PIT1-lineage neoplasms displayed larger cells with expanded intercellular spacing and disorganized spatial arrangements.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"200"},"PeriodicalIF":5.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologic depletion of border-associated macrophages worsens disease in a mouse model of meningitis.","authors":"Susanne Dyckhoff-Shen, Ilias Masouris, Hans-Walter Pfister, Stefanie Völk, Sven Hammerschmidt, Matthias Klein, Uwe Koedel","doi":"10.1186/s40478-025-02126-5","DOIUrl":"10.1186/s40478-025-02126-5","url":null,"abstract":"<p><p>Pneumococcal infection of the leptomeninges triggers a strong inflammatory response, contributing to tissue damage and adverse outcome in meningitis. While border-associated macrophages (BAM) are thought to initiate immune responses against pathogens, their exact role in pneumococcal meningitis (PM) - especially at later stages - remains unclear. This study examined the impact of BAM depletion on disease progression. Mice received intracisternal injections of clodronate liposomes (CL) to deplete BAM, followed three days later by intracisternal infection with Streptococcus pneumoniae. At 18 h post-infection, CL-treated mice exhibited clinical signs similar to controls treated with phosphate-buffered saline liposomes (PBSL). However, CL-treated mice had lower cerebrospinal fluid leukocyte counts, increased expression of brain immune mediators, and elevated plasma levels of neuronal damage (NEFL) and astrocyte activation (S100B) markers. Over a 42-h observation period - during which ceftriaxone therapy was started 18 h post-infection - CL-treated mice showed significantly worse outcomes: 9 of 12 reached termination criteria versus 1 of 9 PBSL-treated mice. This correlated with more severe neuropathology, higher bacterial loads, and persistent inflammation. Notably, infection with a pneumolysin-deficient mutant conferred strong protection against disease aggravation caused by macrophage depletion, whereas caspase-1 inhibition - despite its known immunosuppressive effects in experimental PM - did not. These findings underscore a critical immunoregulatory role for BAM in PM, particularly in resolving rather than initiating inflammation. Their absence exacerbates disease severity, mainly due to increased bacterial proliferation and elevated levels of bacterial toxins.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"191"},"PeriodicalIF":5.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer's disease mouse model.","authors":"David Ramonet, Anna Daerr, Martin Hallbeck","doi":"10.1186/s40478-025-02096-8","DOIUrl":"10.1186/s40478-025-02096-8","url":null,"abstract":"<p><p>Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD. Despite growing evidence for retromer dysfunction in AD, its role in synaptic pathology and neuroinflammation remains incompletely understood. Here, we investigate the acute molecular effects of retromer stabilization in the 5xFAD mouse model of AD using the pharmacological chaperones R55 and R33, previously identified to enhance VPS35 stability. Following intracranial stereotaxic injections, we performed transcriptomic profiling, quantitative histology, and immunohistochemistry to assess synaptic function, neuroinflammation, and endosomal trafficking. Our findings reveal that retromer stabilization reverses multiple AD-associated molecular changes. R55 treatment significantly reduced Aβ-related pathology, normalized synaptic gene expression, and restored long-term potentiation (LTP)-associated pathways, including Gria1 (AMPA receptors), Grip1, and semaphorin/plexin signaling. Additionally, retromer stabilization counteracted dysregulated calcium signaling by modulating Ryr2 and L-type calcium channel expression. Beyond synaptic effects, we observed broad transcriptional and structural changes in the endosomal system. Notably, R55 treatment decreased VPS13 family gene expression, implicated in membrane contact site regulation, while increasing RAB7 levels, suggesting enhanced late-endosomal recycling. VPS35-positive vesicles were redistributed away from the nucleus, indicating restored intracellular trafficking dynamics. In the neuroinflammatory domain, retromer stabilization modulated microglial activation, shifting towards a profile characterized by balanced pro-inflammatory (Il1, Nfkb2) and anti-inflammatory (Il4r, Il13ra1, Stat6) markers, consistent with disease-associated microglia (DAM) phenotypes. Together, these findings demonstrate that retromer dysfunction contributes to key AD pathologies, including synaptic dysfunction and neuroinflammation, and that pharmacological retromer stabilization can restore cellular homeostasis. Given that 5xFAD mice lack direct VPS35 mutations, our results suggest that retromer-targeting strategies may be applicable to both familial and sporadic AD, offering a promising therapeutic avenue for modifying disease progression.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"190"},"PeriodicalIF":5.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Therapeutic potential of NGF-enriched extracellular vesicles in modulating neuroinflammation and enhancing peripheral nerve remyelination.","authors":"Hancheol Yeo, Yoo Jung Kim, Jaekwon Seok, Yeonjoo Kwak, Soo Bin Jang, Na Hee Lim, Kwonwoo Song, Junghoon Lee, Min Chul Cho, Soo Woong Kim, Ssang-Goo Cho","doi":"10.1186/s40478-025-02108-7","DOIUrl":"10.1186/s40478-025-02108-7","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"189"},"PeriodicalIF":5.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of a tear fluid-derived protein biomarker signature in patients with amyotrophic lateral sclerosis.","authors":"Lena-Sophie Scholl, Antonia F Demleitner, Jenny Riedel, Seren Adachi, Lisa Neuenroth, Clara Meijs, Laura Tzeplaeff, Lucas Caldi Gomes, Ana Galhoz, Isabell Cordts, Christof Lenz, Michael Menden, Paul Lingor","doi":"10.1186/s40478-025-02109-6","DOIUrl":"10.1186/s40478-025-02109-6","url":null,"abstract":"<p><p>The diagnosis of Amyotrophic Lateral Sclerosis (ALS) remains challenging, particularly in early stages, where characteristic symptoms may be subtle and nonspecific. The development of disease-specific and clinically validated biomarkers is crucial to optimize diagnosis. Here, we explored tear fluid (TF) as a promising ALS biomarker source, given its accessibility, anatomical proximity to the brainstem as an important site of neurodegeneration, and proven discriminative power in other neurodegenerative diseases. Using a discovery approach, we profiled protein abundance in TF of ALS patients (n = 49) and controls (n = 54) via data-independent acquisition mass spectrometry. Biostatistical analysis and machine learning identified differential protein abundance and pathways in ALS, leading to a protein signature. These proteins were validated by Western blot in an independent cohort (ALS n = 51; controls n = 52), and their discriminatory performance was assessed in-silico employing machine learning. 876 proteins were consistently detected in TF, with 106 differentially abundant in ALS. A six-protein signature, including CRYM, PFKL, CAPZA2, ALDH16A1, SERPINC1, and HP, exhibited discriminatory potential. We replicated significant differences of SERPINC1 and HP levels between ALS and controls across the cohorts, and their combination yielded the best in-silico performance. Overall, this investigation of TF proteomics in ALS and controls revealed dysregulated proteins and pathways, highlighting inflammation as a key disease feature, strengthening the potential of TF as a source for biomarker discovery.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"187"},"PeriodicalIF":5.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optineurin deficiency disrupts phosphorylated tau proteostasis and clusterin expression in human neurons.","authors":"Zachary M Augur, Garrett M Fogo, Mason R Arbery, Andrew M Stern, Courtney R Benoit, Yi-Chen Hsieh, Tracy L Young-Pearse","doi":"10.1186/s40478-025-02103-y","DOIUrl":"10.1186/s40478-025-02103-y","url":null,"abstract":"<p><p>Optineurin (OPTN) is an autophagy adaptor protein involved in selective autophagy, including aggrephagy and mitophagy. Pathogenic mutations in OPTN have also been linked to amyotrophic lateral sclerosis, frontotemporal dementia, and glaucoma, supporting its role in the etiology of neurodegenerative diseases. Despite its established biological roles, knowledge about its potential contribution to Alzheimer's disease (AD) pathology and neuronal functioning is lacking. AD is characterized by the accumulation of extracellular amyloid-β plaques and intracellular phosphorylated tau (pTau) tangles, with dysfunction in the autophagy-lysosomal pathway exacerbating tau pathology and impairing proteostasis. To investigate the role of OPTN in neuronal proteostasis and AD, we utilized induced pluripotent stem cell-derived neuron (iN) and astrocyte (iA) models. Analyses revealed a significant negative correlation between OPTN and specific pTau epitopes in neurons, as well as a decrease in OPTN protein abundance in brain tissues of individuals with AD. Given these findings, we generated OPTN knockout (KO), heterozygous, and wildtype iNs and iAs using CRISPR/Cas9 editing of iPSCs in two genetic backgrounds. Loss of OPTN in iNs increased specific pTau proteoforms without substantially affecting autophagy processes or mitochondrial respiration. Despite no clear effect on mitochondrial function, several mitochondrial proteins, including OXCT1, were enriched in an unbiased analysis of the OPTN interactome in iNs, as well as proteins involved in intracellular trafficking. Proteomic analyses further identified intracellular clusterin, an AD risk gene, as significantly upregulated in OPTN KO iNs, suggesting OPTN may influence its intracellular processing. Our model system demonstrates modest roles for OPTN in certain neuronal biological processes and potential implications for AD pathogenesis. These findings also suggest that OPTN may exhibit functional redundancy with other autophagy adaptor proteins in human neurons, leading to relatively mild phenotypic changes with complete loss of OPTN.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"188"},"PeriodicalIF":5.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering transcriptomic changes in chemobrain: a comprehensive review.","authors":"Tusar Kanta Acharya, Yuan Pan, Peter M Grace, Cobi J Heijnen, Rajasekaran Mahalingam","doi":"10.1186/s40478-025-02102-z","DOIUrl":"https://doi.org/10.1186/s40478-025-02102-z","url":null,"abstract":"<p><p>Chemotherapy-induced cognitive impairments (CICI), colloquially known as \"chemobrain,\" represents a profound and debilitating side effect experienced by a significant number of cancer survivors, impacting their memory, multitasking, and quality of life. This review critically evaluates the molecular mechanisms underlying CICI, with a particular focus on the insights gained from transcriptomic analyses. As cancer incidence rises globally, understanding the complex interplay between chemotherapy agents and their cognitive repercussions becomes increasingly vital. Key mechanisms implicated in CICI include blood-brain barrier disruption, neuroinflammation, and oxidative stress as a result of various chemotherapy treatments, such as doxorubicin, cisplatin, and paclitaxel. We delve into advanced transcriptomic methodologies including RNA sequencing, cDNA microarrays, and single-cell transcriptomics that elucidate the alteration in gene expression profiles associated with CICI and provide a deeper understanding of the underlying pathophysiological processes. Furthermore, we emphasize the importance of developing comprehensive single-cell atlases and employing spatial transcriptomics to uncover cellular heterogeneity and the spatial dynamics of gene expression across different brain regions. This review consolidates the existing literature on the transcriptomic profile of CICI, highlighting potential genes and pathways while suggesting future research avenues aimed at mitigating cognitive dysfunction. Ultimately, integrating transcriptomic findings with clinical insights is essential for the development of targeted, personalized interventions, thereby improving cognitive health and overall quality of life for cancer survivors dealing with long-term impacts of their treatment.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"186"},"PeriodicalIF":5.7,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the intricate dynamics of the interplay between triple-negative breast cancer cells and the blood-brain barrier endothelium.","authors":"Ana Rita Garcia, Ana Rita Vaz, Rui Malhó, Hugo M Botelho, Inês Figueira, Maria Alexandra Brito","doi":"10.1186/s40478-025-01985-2","DOIUrl":"https://doi.org/10.1186/s40478-025-01985-2","url":null,"abstract":"<p><p>Brain metastases (BM) critically reduce breast cancer (BC) patients' survival. Extravasation is pivotal for BM development, but the underlying events at the blood-brain barrier (BBB) remain elusive. We aimed to unravel the players and mechanisms governing BC cells (BCCs)-BBB interaction. For that, mixed cultures of human brain microvascular endothelial cells (HBMECs), mimicking the BBB, and brain-tropic triple-negative BCCs (MDA-MB-231 Br4), or non-brain-tropic (MDA-MB-231) or non-metastatic cells (MCF-7) were established. Temporal and spatial analysis of BCCs-BBB interactions (live-cell imaging automated microscopy), and assessments of endothelial-to-mesenchymal transition (EndMT) markers, transcription factors, cytoskeletal proteins, and morphology (immunocytochemistry) were performed. BBB integrity (permeability, transendothelial electrical resistance) and endothelial migration (wound-healing) were also assessed. Our results revealed that contrasting with non-metastatic and non-brain-tropic cells, BCCs quickly developed an invasive, migratory phenotype, characterized by invadopodium formation and reduced roundness. Spatial analysis showed different positioning of BCCs relative to the BBB endothelium over time, with 14% of BCCs transmigrated after 3 h, compromising BBB integrity through endothelial holes, reduced tightness, and increased permeability. Prior to transmigration, alterations in adhesion markers (E-selectin, ICAM-1, CD24, CD34, β3-integrin, Sialyl-Lewis X) were observed. EndMT was also evident by decreased endothelial (β-catenin and pan cytokeratin) and increased mesenchymal (vimentin, neuronal-cadherin, Slug, ZEB1) markers, elongation (RhoA, α-SMA), nuclear deformation, and migratory capacity. Caveolin-1 silencing in HBMEC decreased BCCs transmigration. This study reveals significant BBB phenotypic and structural changes, facilitating both paracellular and transcellular BCCs transmigration. These findings provide advanced understanding of BCCs trafficking across the BBB, aiding strategy development to prevent extravasation and BM.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"185"},"PeriodicalIF":5.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}