Neuro-oncology最新文献

{"title":"Applications of artificial intelligence and advanced imaging in pediatric diffuse midline glioma.","authors":"Atlas Haddadi Avval, Suneel Banerjee, John Zielke, Benjamin H Kann, Sabine Mueller, Andreas M Rauschecker","doi":"10.1093/neuonc/noaf058","DOIUrl":"10.1093/neuonc/noaf058","url":null,"abstract":"<p><p>Diffuse midline glioma (DMG) is a rare, aggressive, and fatal tumor that largely occurs in the pediatric population. To improve outcomes, it is important to characterize DMGs, which can be performed via magnetic resonance imaging (MRI) assessment. Recently, artificial intelligence (AI) and advanced imaging have demonstrated their potential to improve the evaluation of various brain tumors, gleaning more information from imaging data than is possible without these methods. This narrative review compiles the existing literature on the intersection of MRI-based AI use and DMG tumors. The applications of AI in DMG revolve around classification and diagnosis, segmentation, radiogenomics, and prognosis/survival prediction. Currently published articles have utilized a wide spectrum of AI algorithms, from traditional machine learning and radiomics to neural networks. Challenges include the lack of cohorts of DMG patients with publicly available, multi-institutional, multimodal imaging and genomics datasets as well as the overall rarity of the disease. As an adjunct to AI, advanced MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and Magnetic Resonance Spectroscopy (MRS), as well as positron emission tomography (PET), provide additional insights into DMGs. Establishing AI models in conjunction with advanced imaging modalities has the potential to push clinical practice toward precision medicine.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1419-1433"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557457","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":"Multiplexed epigenetic memory editing using CRISPRoff sensitizes glioblastoma to chemotherapy.","authors":"Katie Lin, Christopher Zou, Akane Hubbard, Sasha Sengelmann, Laine Goudy, I-Ching Wang, Rohit Sharma, Joanna Pak, Kyla Foster, Tomoko Ozawa, John F de Groot, Joanna Phillips, Harish N Vasudevan, David R Raleigh, Alexander Marson, Niren Murthy, Luke A Gilbert, Mitchel S Berger, S John Liu","doi":"10.1093/neuonc/noaf055","DOIUrl":"10.1093/neuonc/noaf055","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) carries a poor prognosis, and new therapeutic strategies are necessary to improve outcomes for patients with this disease. Alkylating chemotherapies including temozolomide (TMZ) and lomustine (CCNU) are critical for treating GBM, but resistance mechanisms, including hypomethylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter, undermine treatment. CRISPRoff is a programmable epigenetic memory editor that can induce stable and heritable gene silencing after transient delivery, and we hypothesize that CRISPRoff could potentiate the activity of TMZ and CCNU through long-term suppression of target genes.</p><p><strong>Methods: </strong>We transiently delivered CRISPRoff mRNA along with sgRNAs against target genes using both electroporation and lipid nanoparticles (LNPs) into established GBM cell lines, patient-derived primary GBM cultures, and orthotopic GBM xenografts. Gene repression, specificity, and stability were measured by RT-qPCR, Western blot, bisulfite sequencing, and RNA sequencing. Sensitivity to chemotherapies was measured by cell viability dose-response, microscopy, and bioluminescence imaging. Genome-wide mapping of CCNU sensitizers was performed using CRISPRi screens.</p><p><strong>Results: </strong>CRISPRoff induced complete suppression of MGMT and sensitization to TMZ that was stable for over 8 months of continuous cell propagation. GBM orthotopic tumors treated with CRISPRoff against MGMT demonstrated sensitivity to TMZ in vivo, and CRISPRoff delivery resulted in chemosensitivity in patient-derived primary GBM. Genome-wide CRISPRi screens identified combinatorial genetic vulnerabilities (BRIP1, FANCE) that were targetable by multiplexed CRISPRoff to achieve sensitization to CCNU.</p><p><strong>Conclusion: </strong>Transient delivery of a site-specific epigenetic memory can induce stable, complete, and multiplexed suppression of target genes for therapeutic application in GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1443-1457"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493152","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":"Identification of urinary metabolic biomarkers for histone 3 lysine27-to-methionine mutation diagnosis in brainstem gliomas.","authors":"Xiaoou Li, Wei Sun, Zhengguang Guo, Feng Qi, Tian Li, Yujin Wang, Mingxin Zhang, Aiwei Wang, Zhuang Jiang, Luyang Xie, Yiying Mai, Yi Wang, Zhen Wu, Nan Ji, Yang Zhang, Liwei Zhang","doi":"10.1093/neuonc/noaf038","DOIUrl":"10.1093/neuonc/noaf038","url":null,"abstract":"<p><strong>Background: </strong>Brainstem gliomas (BSGs) harboring a histone 3 lysine27-to-methionine (H3K27M) mutation represent one of the deadliest brain tumors with a dismal prognosis, as they exhibit a much worse response to therapy compared to the wildtype BSGs. Early noninvasive recognition of the H3K27M mutation is paramount for clinical decision-making in treating BSGs.</p><p><strong>Methods: </strong>Plasma and urine samples were prospectively collected from BSG patients before biopsy or surgical resection and were chronologically divided into discovery, test, and validation cohorts. Utilizing the discovery and test cohort samples, an untargeted metabolomic strategy was exploited to identify candidate metabolite biomarkers, related to the H3K27M mutation. The candidate biomarkers were validated in the validation cohort with a targeted metabolomic method.</p><p><strong>Results: </strong>Differential metabolomic profiles were detected between the H3K27M-mutant and wild-type BSGs in both the plasma and urine, the metabolomic changes were more dramatic in urine than in plasma. After rigorous screening for candidate biomarkers and validation with a targeted metabolomic approach, 3 metabolites, nomilin, Lys-Leu, and Hawkinsin, emerged as significantly elevated biomarkers in H3K27M-mutant BSG urine samples. The biomarker panel combining the 3 metabolites had a diagnostic area under the curve (AUC) of approximately 75%. Furthermore, the biomarker panel improved the prediction accuracy of radiomics/clinical models to an AUC value as high as 93.38%.</p><p><strong>Conclusions: </strong>A urinary metabolite biomarker panel that exhibited high accuracy for noninvasive prediction of the H3K27M mutation status in BSG patients was identified. This panel has the potential to improve the predictive performance of current radiomics models or clinical features.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1536-1549"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414853","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":"Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth.","authors":"Graziella Ribeiro de Sousa, Annaliese J Calzadilla, Enrique Grimaldo, Andrew M Donson, Lays Martin Sobral, Kendra M Jones, Tian Liu, Vladimir Amani, Sujatha Venkataraman, Nathan A Dahl, Jean M Mulcahy Levy, Tzu Phang, Rajeev Vibhakar, Todd Hankinson, Michael Handler, Elvis Terci Valera, Nicholas K Foreman, Andrea M Griesinger","doi":"10.1093/neuonc/noaf029","DOIUrl":"10.1093/neuonc/noaf029","url":null,"abstract":"<p><strong>Background: </strong>Posterior fossa molecular subtype A (PFA) ependymoma occurs in young children and is the deadliest subtype of pediatric ependymoma. High-risk subtypes with chromosome 1q + and/or 6q- exhibit significantly poorer outcomes compared to wild-type PFA. However, 50% of wild-type PFA patients relapse and there is a high risk of gaining chromosome 1q at recurrence. We previously found constitutively active NF-κB, through loss of LDOC1, led to chronic IL-6 secretion and an overall immunosuppressive tumor microenvironment in the higher-risk wild-type PFA ependymoma subset (PFA1).</p><p><strong>Methods: </strong>In this study, we delineate the mechanistic consequences of LDOC1 loss in PFA1, using our PFA ependymoma in vitro and in vivo models under normoxia and hypoxia conditions.</p><p><strong>Results: </strong>We noted chromatin compaction by H3K27me3 at the LDOC1 loci results in loss of LDOC1 gene expression. Restoration of LDOC1 was sufficient to reduce proliferation, NF-κB signaling, and a significant decrease in IL-6 secretion. Furthermore, tumors implanted with LDOC1-transduced cells in vivo were out competed by non-transduced cells, suggesting loss of LDOC1 is required for PFA tumor growth.</p><p><strong>Conclusion: </strong>These findings shed further light on the biology of PFA1 ependymoma and the role LDOC1 loss has on the tumor and immunobiology of high-risk pediatric ependymoma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1597-1610"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123265","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":"Rethinking neurocognitive outcomes in adult survivors of childhood medulloblastoma: Progress and unmet challenges.","authors":"Sijia Liu, Jialao Ma","doi":"10.1093/neuonc/noaf051","DOIUrl":"10.1093/neuonc/noaf051","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1409-1411"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030228","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":"GBMPurity: A machine learning tool for estimating glioblastoma tumor purity from bulk RNA-sequencing data.","authors":"Morgan P H Thomas, Shoaib Ajaib, Georgette Tanner, Andrew J Bulpitt, Lucy F Stead","doi":"10.1093/neuonc/noaf026","DOIUrl":"10.1093/neuonc/noaf026","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) presents a significant clinical challenge due to its aggressive nature and extensive heterogeneity. Tumor purity, the proportion of malignant cells within a tumor, is an important covariate for understanding the disease, having direct clinical relevance or obscuring signal of the malignant portion in molecular analyses of bulk samples. However, current methods for estimating tumor purity are nonspecific and technically demanding. Therefore, we aimed to build a reliable and accessible purity estimator for GBM.</p><p><strong>Methods: </strong>We developed GBMPurity, a deep learning model specifically designed to estimate the purity of IDH-wild type primary GBM from bulk RNA-sequencing (RNA-seq) data. The model was trained using simulated pseudobulk tumors of known purity from labeled single-cell data acquired from the GBmap resource. The performance of GBMPurity was evaluated and compared to several existing tools using independent datasets.</p><p><strong>Results: </strong>GBMPurity outperformed existing tools, achieving a mean absolute error of 0.15 and a concordance correlation coefficient of 0.88 on validation datasets. We demonstrate the utility of GBMPurity through inference on bulk RNA-seq samples and observe reduced purity of the proneural molecular subtype relative to the classical, attributed to the increased presence of healthy brain cells.</p><p><strong>Conclusions: </strong>GBMPurity provides a reliable and accessible tool for estimating tumor purity from bulk RNA-seq data, enhancing the interpretation of bulk RNA-seq data and offering valuable insights into GBM biology. To facilitate the use of this model by the wider research community, GBMPurity is available as a web-based tool at: https://gbmdeconvoluter.leeds.ac.uk/.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1458-1473"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075033","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":"Tumor cells upregulate neurotransmitter GABA in the choroid plexus through STAT6-Bestrophin1 signaling, promoting leptomeningeal dissemination.","authors":"Diganta Das, Mukund Iyer, Brooke Nakamura, Saman Sedighi, Angela Hsu, Camelia Danilov, Peter S LaViolette, Jennifer Connelly, Frances Chow, Josh Neman","doi":"10.1093/neuonc/noaf027","DOIUrl":"10.1093/neuonc/noaf027","url":null,"abstract":"<p><strong>Background: </strong>Leptomeningeal dissemination (LMD) occurs when tumor cells interact with choroid plexus epithelium (CPE) to gain access to cerebrospinal fluid (CSF) in the brain's meninges and ventricular system. This disease is particularly devastating for patients due to our limited understanding and few therapeutic options. The leptomeningeal CSF is a nutritionally deprived microenvironment for tumor cells. Despite this, LMD tumor cells survive by taking up and metabolizing the neurotransmitter gamma-aminobutyric acid (GABA) from the CSF. However, we currently lack evidence on how CSF-GABA levels are altered and how tumor cells communicate with the CPE to increase GABA levels in the LMD microenvironment. Herein, we examined the interactions between CPEs and tumor cells that make CSF more hospitable to LMD growth.</p><p><strong>Methods: </strong>Primary choroid plexus, breast cancer cells, and patient-derived breast and lung-to-brain metastatic cells, are utilized in in vivo metastatic /LMD modeling along with signal transducer and activator of transcription 6 (STAT6) inhibitor and IL13 gene knockdown.</p><p><strong>Results: </strong>We show breast and lung cancer cells derived-IL13 activates STAT6 signaling in choroid plexus. Subsequently, choroid plexus upregulates GABA-synthesizing enzyme GAD67 and GABA-permeable channel Bestrophin1, all leading to elevated neurotransmitter GABA levels in the CSF. Moreover, we show a significant reduction of Bestrophin1 in choroid plexus when tumor-derived IL13 is knocked down or when treated with brain permeable STAT6 specific inhibitor AS1517499, leading to increased survival.</p><p><strong>Conclusions: </strong>Overall, these findings reveal a novel STAT6-Bestrophin1-GABA axis in choroid plexus and its therapeutic targeting can lead to favorable outcomes in leptomeningeal disease.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1476-1490"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067049","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":"Novel PET RANO BM 1.0 criteria: Regulatory perspectives on new endpoint definitions in brain metastases.","authors":"Francesco Pignatti, Ralf Herold, Pierre Demolis, Ulrich-Peter Rohr","doi":"10.1093/neuonc/noaf067","DOIUrl":"10.1093/neuonc/noaf067","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1407-1408"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034873","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":"Hypofractionated Stereotactic Radiotherapy versus Whole-Brain Radiotherapy following Brain Metastasis Resection - Results of the ESTRON Randomized Phase 2 Trial.","authors":"Rami A El Shafie, Denise Bernhardt, Thomas Welzel, Annabella Schiele, Daniela Schmitt, Paul Thalmann, Sinem Erdem, Tanja Eichkorn, Angela Paul, Kristin Lang, Laila König, Fabian Weykamp, Sebastian Adeberg, Adriane Lentz-Hommertgen, Cornelia Jäkel, Farastuk Bozorgmehr, Michael Thomas, Anja Sander, Meinhard Kieser, Jürgen Debus, Stefan Rieken","doi":"10.1093/neuonc/noaf182","DOIUrl":"https://doi.org/10.1093/neuonc/noaf182","url":null,"abstract":"<p><strong>Background: </strong>Postoperative radiotherapy improves local control after brain metastasis (BM) resection. Whole-brain radiotherapy (WBRT) reduces recurrence risk but impairs neurocognition. Hypofractionated stereotactic radiotherapy of the cavity (HFSRT) may offer equivalent tumor control with reduced toxicity. ESTRON is the first randomized trial comparing post-operative HFSRT and WBRT.</p><p><strong>Methods: </strong>This single-center phase 2 trial randomized 56 patients with resected BM to receive HFSRT (35 Gy in 7 fractions) or WBRT (30 Gy in 10 fractions). Patients could have ≤10 additional unresected BMs. The primary endpoint was intracranial progression-free survival (ic-PFS). Secondary endpoints included local control (LC), overall survival (OS), leptomeningeal disease (LMD), and toxicity.</p><p><strong>Results: </strong>Fifty-four patients were evaluable (n=27 per arm). At 24.7 months median follow-up, 12-month ic-PFS was 44.4% (HFSRT) versus 59.3% (WBRT) (HR 1.72, p=0.080). Median ic-PFS was 4.7 vs. 15.0 months. LC at 24 months was 94.1% (HFSRT) vs. 85.4% (WBRT) (HR 0.41, p=0.433). One-year OS was 63.0% (HFSRT) vs. 77.8% (WBRT), with no significant difference in median OS (17.8 vs. 27.0 months; HR 1.09, p=0.336). One-year risk of LMD was 27.0% (HFSRT, predominantly outside the irradiated field) vs. 8.7% (WBRT) (log-rank p=0.03). Treatment-related adverse events were more frequent with WBRT (115 vs. 54 events), including 19% vs. 11% grade 3 events, and poorer neurocognitive performance.</p><p><strong>Conclusions: </strong>Survival was similar for HFSRT and WBRT, while WBRT trended towards better ic-PFS. HFSRT showed substantially lower toxicity and better neurocognitive preservation, however a higher risk of LMD. Risks and benefits should be weighed individually when determining post-operative treatment for BM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760625","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":"Glioma-Associated Microglia Potentiate Neuronal Hyper-Excitability in the Glioma Environment.","authors":"Jaeseung Yei, Na Kyeong Lee, Seungmin Ryu, Seong-Eun Ryu, Juheon Lee, Taeyoung Park, Yoonyi Jeong, Rian Kang, Ho-Keun Kwon, Seong-Gi Kim, Jong-Chan Park, Chun Gwon Park, Minah Suh","doi":"10.1093/neuonc/noaf181","DOIUrl":"https://doi.org/10.1093/neuonc/noaf181","url":null,"abstract":"<p><strong>Background: </strong>Hyper-excitable neurons are observed in the glioma brain, contributing to the notorious nature of glioma. It is well established that microglia can modulate neuronal excitability through crosstalk via P2RY12. However, the role of microglia in glioma environments remains poorly understood. Thus, this study aimed to investigate whether loss of microglial P2RY12 could contribute to hyper-excitable neurons within the glioma environment.</p><p><strong>Methods: </strong>Using two distinct tumor models and normal Thy1-GCaMP6f mice, spontaneous neuronal activity was imaged in the peritumor region with an in vivo 2-photon microscope. Neuronal calcium activity was then compared to expression level of microglial P2RY12. Neuronal activity was further quantified after administering a microglial blocker and compared across different tumor models and cortical regions of a glioma mouse model.</p><p><strong>Results: </strong>Our findings revealed that hyper-excitable neurons were exclusively observed in cortical regions surrounding glioma tissues. In the glioma environment, microglia exhibited significantly reduced expression of P2RY12, a receptor known to modulate neuronal activity via negative feedback control. In contrast, neuronal excitability and microglial P2RY12 expression relatively remained same to the control in environments of a brain metastasis model. Furthermore, blocking microglial P2RY12 enhanced spontaneous neuronal activity in both the brain metastasis model and distal regions of glioma tumors, effectively replicating the functional loss of P2RY12 observed in glioma conditions.</p><p><strong>Conclusions: </strong>Results of this study support that neuronal hyper-excitability is a unique observation within a peri-glioma environment driven by loss of microglial P2RY12.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753909","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}