Neuroimmunomodulation最新文献

{"title":"Inflammation-Induced Temperature Shifts and Mitochondrial Function: Rethinking Biomarker Interpretation in Depressive Disorders.","authors":"Alexander Karabatsiakis, Rafael Pfeiffer, Annalena Steinlechner, Karin de Punder","doi":"10.1159/000552988","DOIUrl":"10.1159/000552988","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"300-303"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Statement: Tetrahydrocurcumin Provides Neuroprotection in Experimental Traumatic Brain Injury and the Nrf2 Signaling Pathway as a Potential Mechanism.","authors":"","doi":"10.1159/nim/adxag006","DOIUrl":"https://doi.org/10.1159/nim/adxag006","url":null,"abstract":"<p><p>The article \"Tetrahydrocurcumin Provides Neuroprotection in Experimental Traumatic Brain Injury and the Nrf2 Signaling Pathway as a Potential Mechanism.\" [Neuroimmunomodulation. 2018;24(6):348-355. https://doi.org/10.1159/000487998] by Guan Wei, Bingji Chen, Qingjiang Lin, Yasong Li, Liangqin Luo, Hefan He, and Huangde Fu has been retracted by the Publisher and the Editor.After publication, concerns were identified regarding image duplication within this article and between Figures 2 and 3 the above article and a previously published article [1]. Specifically,Figure 3e Nrf2 is duplicated as Figure 3g Nrf2 in this article.Figure 2a of this article overlaps with Figure 2a of [1].Figure 3a of this article overlaps with Figure 5a of [1].Figure 3d of this article overlaps with Figure 5d of [1].Figure 3e and 3g Nrf2 of this article are presented as Nrf2 in Figure 5e of [1].When asked to comment, the corresponding author stated that this image duplication may be due to use of shared experimental equipment. Following editorial review of the concerns and the response, it was concluded that these concerns impacted the reliability of the results in the article and therefore, the article has been retracted.The authors agree to the retraction.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"33 1","pages":"336-337"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between Peripheral and Central Nervous System Myeloid Cells during Aging: Impact for Lade-Life Depression and Alzheimer's Disease.","authors":"Aline Silva de Miranda, Érica Leandro Marciano Vieira, Antonio Lucio Teixeira, Moisés Evandro Bauer","doi":"10.1159/000550781","DOIUrl":"10.1159/000550781","url":null,"abstract":"<p><strong>Background: </strong>Aging is associated with enumerative and functional changes of peripheral innate immune cells, notably myeloid cells (e.g., monocytes/macrophages and neutrophils). Peripheral myeloid cells routinely infiltrate the brain, particularly at the brain borders, influencing cognition, mood, and stress responses.</p><p><strong>Summary: </strong>Here, we review how the dysfunctional crosstalk between circulating myeloid cells and brain cells may contribute to the development of late-life depression and Alzheimer's disease during aging. The aged cerebral microglia (i.e., resident macrophages) exhibit dystrophic morphology and impaired phagocytosis while peripheral myeloid cells expand in number but display functional deficits, including impaired phagocytosis and pro-inflammatory biased response. The peripheral myeloid changes collectively contribute to systemic chronic inflammation and tissue dysfunction. Epigenetic changes and metabolic disruptions, such as altered glucose utilization, exacerbate pro-inflammatory states.</p><p><strong>Key messages: </strong>The cumulative impact of these alterations undermines neuroprotection and facilitates age-related neuropsychiatric conditions, including neurodegenerative diseases and late-life depression. The identification of pro-aging circulating factors and cells could pave the way for new therapeutic strategies aimed at mitigating cognitive decline and improving mood. Targeting myeloid cell metabolism or inflammatory signaling pathways emerges as a promising strategy to mitigate aging-associated neuropsychiatric syndromes.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"101-124"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRP3 Inflammasome Activation in Oxidative Stress: A Key Mechanism Driving Neuroinflammation.","authors":"Crisalde Ramirez-Celis, Ari Misael Martínez-Torres, Julio Morán","doi":"10.1159/000551943","DOIUrl":"10.1159/000551943","url":null,"abstract":"<p><strong>Background: </strong>In acquired and neurodegenerative brain diseases, inflammation-mediated neuronal death contributes to the deterioration of neurological deficits in patients. In the innate immune system, the NLRP3 inflammasome is a cytosolic complex that regulates the release of proinflammatory cytokines IL-1β and IL-18, thereby amplifying the inflammatory response and neuronal damage. Consequently, inhibition of the NLRP3 inflammasome represents a promising pharmacological strategy to limit inflammation across multiple pathologies. Oxidative stress is a common hallmark of these pathological conditions that contribute to neuronal death and influence NLRP3 activation. Despite the implications of these events, the molecular mechanisms underlying this activation remain poorly understood.</p><p><strong>Summary: </strong>In this review, we describe the key features of the NLRP3 inflammasome and explore the role of oxidative stress in its activation. Additionally, we discuss the evidence supporting the regulation of inflammasome activity by antioxidant molecules.</p><p><strong>Key message: </strong>Understanding the role of oxidative stress in NLRP3-mediated inflammation offers promising advantages for therapeutic strategies to reduce neuronal death.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"236-263"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Lipid Road to Neuroimmunology: Fatty Acids Linking Immune and Nervous Systems.","authors":"Isabelle Moraes-de-Souza, Bianca Portugal Tavares de Moraes, Renan Muniz-Santos, Gabrielle Lacerda de Souza Gomes-Reis, Francisco da Silva Dos Santos, Juliana Santiago Guedes Saraiva, Marina Ferreira-Costa, Carolina Medina Coeli da Cunha, Bárbara Albuquerque Carpinter, Adriana Ribeiro Silva, Cassiano Felippe Gonçalves-de-Albuquerque","doi":"10.1159/000550168","DOIUrl":"10.1159/000550168","url":null,"abstract":"<p><strong>Background: </strong>Neuroimmunology focuses on the two-way communication between the nervous and immune systems, a crucial relationship that maintains the body's internal balance. Disruptions in this neural-immune axis are associated with several disorders.</p><p><strong>Summary: </strong>Fatty acids, as bioactive molecules, can modulate both neural and immune functions. Saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) have opposite effects: SFAs promote inflammation and are associated with neurodegenerative diseases and cognitive impairment, whereas PUFAs exhibit anti-inflammatory and neuroprotective properties. The balance between SFAs and PUFAs is key in regulating neuroimmune interactions.</p><p><strong>Key messages: </strong>Fatty acid receptors act as essential molecular sensors, connecting lipid signaling to both immune and neural outcomes, and their activation or inhibition influences cytokine production and neuron survival. Due to their role in these pathways, targeting fatty acid interactions to control inflammation and promote neural repair represents a promising strategy for neurological disease therapies. This review examines how fatty acids influence neuroimmune cells and may pave the way for the development of new therapeutic approaches.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"45-74"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12991812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanism of Carboxypeptidase E Regulating NLRP3 Inflammasome Signaling in the Pathogenesis of Depression-Like Behaviors in Mice.","authors":"Xili Yang, Zhimin Qi, Song Huang, Xinyan Zhao, Yueyang You, Huiying Liu, Shuchun Yu, Xiaohong Du, Fan Xiao","doi":"10.1159/000553608","DOIUrl":"10.1159/000553608","url":null,"abstract":"<p><strong>Introduction: </strong>Depression is a common mental disease. Carboxypeptidase E (CPE) may be a therapeutic target for depression. This study aimed to investigate whether CPE regulates NOD-like receptor protein 3 (NLRP3) inflammasome signaling and affects pyroptosis, thereby improving cellular damage and depression-like behaviors in depressed mice.</p><p><strong>Methods: </strong>A mouse model of depression-like behavior was established with chronic unpredictable mild stress (CUMS) and treated with Lv-oe-CPE, an NLRP3 inflammasome activator (nigericin), or an NLRP3 inflammasome inhibitor (MCC950). Anxiety- and depression-like behaviors were assessed through open field test, forced swim test, tail suspension test, and sucrose preference test. Cellular damage in the hippocampal CA1 region was evaluated with H&E and Nissl staining. CPE, gasdermin D-N (GSDMD-N), NLRP3, cleaved caspase 1, apoptosis-associated spot-like protein (ASC), oxidative stress, interleukin (IL)-1β, and IL-18 levels, and GSDMD-N-positive cells were assessed with Western blot, kits, and immunohistochemistry.</p><p><strong>Results: </strong>CPE was downregulated in the hippocampal CA1 region of CUMS mice, and its reexpression attenuate depression-like behaviors. CPE overexpression suppressed NLRP3, cleaved caspase 1, ASC, IL-1β, and IL-18 levels in the hippocampal CA1 region. NLRP3 inflammasome inactivation alleviated CA1 cellular damage to inhibit depressive-like behaviors, whereas its activation reversed the improving effect of CPE. CPE inactivated NLRP3 inflammasomes, thereby attenuating cell pyroptosis in the hippocampal CA1 region.</p><p><strong>Conclusions: </strong>CPE is downregulated in the hippocampal CA1 region of the mouse model of depression-like behavior. CPE overexpression can inhibit NLRP3 inflammasome activation and then reduce pyroptosis, hence repairing cellular damage in the hippocampal CA1 region and eventually suppressing depressive-like behaviors.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"315-335"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenal and Metabolic Hormonal Axes Shape Anti-Tuberculosis Immune Responses in Human Immunodeficiency Virus-Tuberculosis Coinfection.","authors":"María Belén Vecchione, Denise Anabella Giannone, Milagros Victoria Acevedo, Natalia Santucci, Maria Florencia Quiroga","doi":"10.1159/000550045","DOIUrl":"10.1159/000550045","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains a leading cause of mortality worldwide among infectious agents, and HIV increases the risk of developing into active disease. HIV-TB coinfection impairs immune responses, while chronic inflammation and infection-associated stress activate neuroendocrine pathways that deeply impact immune homeostasis. Adrenal steroids such as cortisol, dehydroepiandrosterone (DHEA) and its metabolites, along with metabolic hormones like leptin and adiponectin, have emerged as critical regulators of immune function, although their role in TB pathogenesis, particularly in co-infected individuals, remains underexplored.</p><p><strong>Summary: </strong>This review navigates over current evidence on the neuroendocrine-immune crosstalk in HIV-TB coinfection, focusing on adrenal and metabolic hormonal axes. We first summarize how HIV-driven CD4+ T cell depletion, chronic immune activation, and altered granuloma dynamics predispose individuals to TB reactivation. We then examine findings indicating that TB and HIV disrupt hypothalamic-pituitary-adrenal (HPA) axis homeostasis, leading to elevated cortisol levels, reduced DHEA and its metabolites, and an unfavorable cortisol/DHEA ratio, which correlated with poor immune control and disease severity. Preclinical studies highlight immunomodulatory properties of DHEA derivatives, such as 7-oxo-DHEA (7-OD), which restore Th1 responses, limit Treg expansion, and enhance macrophage antimicrobial activity. Metabolic hormones, particularly leptin and adiponectin, further shape host immunity and energy allocation; their dysregulation in coinfection contributes to wasting, impaired granuloma formation, and increased immune reconstitution inflammatory syndrome (IRIS) risk. Despite compelling preclinical findings, clinical studies on hormonal modulation remain scarce, emphasizing the need for translational research that links endocrinology and infectious disease immunology.</p><p><strong>Key messages: </strong>HIV-TB coinfection creates a neuroendocrine-immune imbalance, with dysregulation of the HPA axis and metabolic hormones contributing to impaired immune control and accelerated disease progression. Adrenal hormones such as DHEA and its metabolite 7-oxo-DHEA show potential as immunomodulatory agents, capable of restoring Th1 responses, limiting Treg expansion, and supporting host-directed therapies. Additionally, leptin and adiponectin emerge as crucial metabolic players that integrate nutritional status and immune activity and may serve as potential biomarkers for TB management. Altogether, integrating endocrine profiling into TB research and advancing the clinical evaluation of hormonal immunomodulators may unlock novel avenues for precision medicine, improving treatment strategies for populations affected by the HIV and TB epidemics.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"34-44"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12880830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autonomic-Immunoinflammatory-Cardiac Interplay during Lipopolysaccharide-Induced Systemic Inflammation.","authors":"Kumari Akanksha, José Javier Reyes-Lagos, Rahul Kumar, Yogender Aggarwal, Rakesh Kumar Sinha","doi":"10.1159/000551764","DOIUrl":"10.1159/000551764","url":null,"abstract":"<p><strong>Introduction: </strong>Lipopolysaccharide (LPS) triggers a complex autonomic-immunoinflammatory-cardiac interplay involving time-dependent dynamics, cytokine pleiotropy, and context-dependent autonomic responses that complicate interpretation. Therefore, the study aimed to evaluate autonomic alterations, cardiac electrical alterations, and the Vagal Neuroimmunomodulation Index (VNIM), and to assess systemic and cardiac inflammatory markers following LPS-induced endotoxemia in a preclinical rat model.</p><p><strong>Methods: </strong>Male Wistar rats were divided into two groups: control and LPS-treated (n = 5 per group). Endotoxemia was induced by intraperitoneal administration of LPS (3 mg/kg), and lead-II electrocardiogram (ECG) signals were recorded after 24 h for heart rate variability (HRV) analysis and ventricular repolarization/morphological analysis (QT, JT, Tpeak-Tend, ST segment, and Q waves). Biochemical analysis, including inflammatory markers, was quantified in plasma and cardiac tissue. The VNIM was obtained as the ratio of vagally mediated HRV to the inflammatory markers.</p><p><strong>Results: </strong>LPS administration resulted in a significant increase in core temperature, tachycardia, and marked reductions in HRV indices, indicating impaired autonomic regulation. LPS-treated rats exhibited significantly higher levels of plasma C-reactive protein, heart IL-6, and leukocyte counts. ECG analysis demonstrated prolonged QT, JT, and Tpeak-Tend intervals, alongside ST-segment depression and Q-wave inversion, indicative of electrical remodeling and myocardial damage. The VNIM index was significantly reduced across all inflammatory markers, demonstrating a breakdown of parasympathetic regulation over immune activation. Correlation analyses revealed significant associations among autonomic, immunoinflammatory, and cardiac parameters.</p><p><strong>Conclusion: </strong>LPS-induced endotoxemia in rats leads to pronounced autonomic and inflammatory dysregulation, accompanied by distinct ECG abnormalities and reduced VNIM. The integration of HRV, cytokine, and ECG profiling provides valuable insight into the autonomic-inflammatory-cardiac interplay during systemic inflammation, supporting their utility in early diagnosis and monitoring of sepsis and related conditions.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"160-172"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurocysticercosis Is the Result of the Interplay between Parasites, Hormones, and Inflammation.","authors":"Marta C Romano, Jesus Angel Aguirre-Pineda, Ninel Castro-Chávez, Lorena Hinojosa, Ricardo A Valdez","doi":"10.1159/000551689","DOIUrl":"10.1159/000551689","url":null,"abstract":"<p><strong>Background: </strong>Parasitic infections of the central nervous system are still a health problem in low- and middle-income countries and due to international travels and migration can affect even opulent countries. Parasites can modulate host immunity to ensure their long-term survival without inflammatory symptoms; therefore, infection of the brain parenchyma by Taenia solium cysticerci (parenchymal neurocysticercosis) may be asymptomatic, or on the other hand lead to severe inflammation that initiates glial activation with production of pro-inflammatory cytokines, with mild to severe neurological symptoms. Besides, when cysticerci are localized in the ventricles or in the subarachnoid space (extraparenchymal neurocysticercosis) severe symptoms and treatment difficulties occur.</p><p><strong>Summary: </strong>Here we review how the nervous, the immune, and the endocrine systems interact with T. solium and crassiceps cysticerci and influence the course and individualities of the disease that the parasites trigger in humans and animals. For example, a clear sexual dimorphism in cysticercosis has been found in experimental models of the disease, but the influence of gender in human patients needs further investigation. The synthesis of steroids by the brain cells and the cysticerci might influence the local immune response elicited by the presence of the parasites. Remarkably, cultured cysticerci can synthesize sex steroids and deoxycorticosterone, suggesting that these parasites can influence the local brain microenvironment, especially by producing dehydroepiandrosterone, estrogens, and androgens, which could modify the immune response. Treatment of neurocysticercosis includes cysticidal drugs and corticosteroids intended to control the inflammation caused by the parasite; however, these steroids represent a double-edged tool due to their side effects during prolonged administration and also because of some beneficial effects for the parasite itself.</p><p><strong>Key messages: </strong>Parasite survival in the host depends on the inflammatory response and the local microenvironment, including steroid hormones that can promote their survival and even their development and proliferation. New strategies should be designed to manage the severe symptoms induced by the chronic presence or the death of parasites and the poor response to treatment that occurs in extraparenchymal neurocysticercosis.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"200-212"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13252922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat Stress-Activated P2X7 Receptor Induces Astrocyte Activation and Regulates Glioma Tumor Microenvironment via Calcium Signaling Pathway.","authors":"Qiang Wang, XiangRui Chen, JiuJiang Zhang, YanGuo Zhang, HeMin Yang","doi":"10.1159/000552781","DOIUrl":"10.1159/000552781","url":null,"abstract":"<p><strong>Introduction: </strong>The effects of adjuvant hyperthermia on glioblastoma-associated astrocytes remain poorly characterized. This study aimed to investigate the role of the purinergic P2X7 receptor, an ATP-gated ion channel, in mediating heat-induced astrocyte activation and its impact on tumor progression.</p><p><strong>Methods: </strong>Primary mouse astrocytes were subjected to heat stress (mild hyperthermia at 42°C). P2X7 signaling was examined using a specific antagonist (A-740003), siRNA-mediated knockdown, and live-cell calcium imaging. Astrocyte activation was evaluated by assessing glial fibrillary acidic protein expression and pro-inflammatory markers. The pro-tumorigenic potential of astrocyte-conditioned medium was tested on U87 glioblastoma cells. An orthotopic mouse model was used to validate the effects of local hyperthermia, with or without P2X7 inhibition.</p><p><strong>Results: </strong>Mild hyperthermia upregulated P2X7 expression in astrocytes and induced a substantial calcium influx, leading to activation of the calcineurin-NFAT pathway. This process promoted a reactive astrocyte phenotype and a pro-tumorigenic secretory profile, enhancing U87 cell proliferation, migration, and invasion. In vivo, mild hyperthermia was associated with increased tumor progression, which was attenuated by pharmacological inhibition of P2X7.</p><p><strong>Conclusion: </strong>Heat stress facilitates glioblastoma progression by activating astrocytes through the P2X7-mediated calcium-calcineurin-NFAT signaling pathway. These findings highlight P2X7 as a potential therapeutic target for optimizing hyperthermia-based strategies in glioblastoma treatment.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"372-389"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}