Journal of integrative neuroscience最新文献

{"title":"Molecular Mechanisms and Potential Biomarkers of Neuropsychiatric Disorders in Parkinson's Disease.","authors":"Wojciech Owecki, Anna Futyma, Olga Kokorniak, Aleksandra Szczech, Bartosz Słowikowski, Joanna Poszwa, Oliwia Szymanowicz, Ulyana Goutor, Paweł P Jagodziński, Wojciech Kozubski, Jolanta Dorszewska","doi":"10.31083/JIN50055","DOIUrl":"10.31083/JIN50055","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common degenerative disease of the central nervous system, characterized by both motor and non-motor disorders. Non-motor disorders include dementia, depression, and anxiety. The prevalence of dementia increases with disease progression, affecting 24-31% of PD patients and up to 75% after 10 years. Furthermore, approximately 50% of PD patients suffer from depression, while anxiety affects around 31% of this population. Molecular factors, including genetic factors, are currently implicated in the manifestation of neuropsychiatric disorders. It is believed that dementia and affective disorders in PD may result from both disturbed homeostasis of proteins such as α-synuclein, amyloid beta, and phosphorylated tau, as well as increased inflammatory processes and impaired neurotransmission. Chronic microglial activation, elevated levels of proinflammatory cytokines, and oxidative stress contribute to the severity of neuroinflammation, which in turn contributes to neuronal dysfunction and synaptic abnormalities. While the effect of pathological proteins in PD primarily involves impairment of dopaminergic neurotransmission, disturbances in the serotonergic, noradrenergic, cholinergic, and glutamatergic systems are also observed. Furthermore, genetic risk factors have been identified in PD patients, including monogenic causes, which are rare in unselected populations. Identifying causative molecular targets in PD is essential for developing therapies for this neurodegenerative disease. In this review, we present current views on the involvement of molecular factors in the development of psychiatric disorders in patients with PD, suggesting that they may have diagnostic and predictive value in the future.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"50055"},"PeriodicalIF":3.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054853","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":"Microenvironmental Regulation of Central Nervous System Myelination and Remyelination.","authors":"Yuxuan Wang, Lingzhen Tan, Lin Lao, Xiaomeng Huang, Sheng Zhang, Haitao Sun","doi":"10.31083/JIN43257","DOIUrl":"10.31083/JIN43257","url":null,"abstract":"<p><p>Both myelination and remyelination in the central nervous system (CNS) rely on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). However, the microenvironment and underlying mechanisms of these two processes are significantly different. Myelination is driven by intrinsic developmental programs, whereas remyelination is triggered as a response to demyelinating injury. These distinct origins shape unique microenvironmental conditions that critically influence the respective processes. The microenvironment comprises, the extracellular matrix (ECM) and cellular components. Neurons, microglia, and astrocytes play stage-specific roles, ensuring proper myelin turnover under physiological conditions and regeneration after demyelination. Dysregulation of the microenvironment represents a critical driver of aberrant myelination and remyelination failure, as well as a key limitation of current pro-regenerative strategies. In this review, we discuss the cellular and molecular basis of microenvironmental regulation, recent advances in pathological microenvironmental alterations across demyelinating diseases (multiple sclerosis and neuromyelitis optica spectrum disorder) and myelin-associated disorders (Alzheimer's disease and ischemic stroke), and emerging pro-remyelination strategies targeting the microenvironment, such as Bruton's tyrosine kinase (BTK) inhibitors and microglia replacement strategies. We provide a non-cell autonomous perspective to advance the understanding of OLs differentiation and CNS remyelination.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"43257"},"PeriodicalIF":3.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054816","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":"Influence of Gait Speed on Spatiotemporal Parameters in Advanced Parkinson's Disease Following Subthalamic Nucleus Deep Brain Stimulation.","authors":"Daniela Sýkorová, Barbora Kolářová, Petr Kolář, David Krahulík, Ahmed Naser Mohamed Afifi, Pavel Otruba, Martin Nevrlý","doi":"10.31083/JIN48076","DOIUrl":"10.31083/JIN48076","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a recognized treatment for advanced PD, yet its impact on gait parameters remains variable. The aim of this prospective study was to evaluate changes in spatiotemporal gait parameters following DBS-STN in patients with advanced PD.</p><p><strong>Methods: </strong>Thirty patients with advanced PD underwent bilateral DBS-STN. Gait assessments were performed preoperatively and three months postoperatively using a pressure-sensitive treadmill under three walking speed conditions (slow, optimal and fast). Spatiotemporal gait parameters (as walking speed, double-stance phase, cadence, step length, stance phase duration) and derived values, such as asymmetry of both step length and stance phase, were analyzed with respect to the clinically better and worse limbs defined in accordance with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS).</p><p><strong>Results: </strong>No significant changes in walking speed, cadence, or double stance phase duration comparing gait characteristics pre- and postoperatively were found. Significant improvements were found in step length for the clinically worse limb at slow and optimal walking speeds and in stance phase duration for the clinically better limb at fast walking speed. Additionally, asymmetry in both step length and stance phase duration decreased at the fast walking speed after stimulation. For all other parameters evaluated in other walking speeds, the differences were not statistically significant.</p><p><strong>Conclusions: </strong>DBS-STN combined with medication had limited overall effects on spatiotemporal gait parameters in patients with advanced PD. However, when the clinically worse and better lower limbs were analyzed separately, selective improvements in step length and stance phase duration, along with reduced gait asymmetry at higher walking speeds were observed. These findings suggest that DBS may modulate specific components of gait control rather than global gait performance, highlighting the importance of individualized assessment in postoperative gait evaluation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"48076"},"PeriodicalIF":3.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054852","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":"<i>Lactobacillus mucosae</i> Reduces Neuronal Oxidative Stress in Alzheimer's Disease via the Regulation of CB2 Signaling.","authors":"Yu Kong, Xinhuang Lv, Yao Yang, Qiyao Li, Conghui Dai, Xiaoou Lin, Jiaming Liu, Jing Li","doi":"10.31083/JIN48598","DOIUrl":"10.31083/JIN48598","url":null,"abstract":"<p><strong>Background: </strong>The probiotic <i>Lactobacillus mucosae</i> has been widely shown to have many positive effects. However, its neuroprotective effects and underlying mechanism in Alzheimer's disease (AD) remain elusive.</p><p><strong>Methods: </strong>Male APP/PS1 mice were treated for 4 weeks with <i>L. mucosae</i> WMU007, followed by the evaluation of cognitive function, neuronal damage, amyloid-β (Aβ) deposition, and Tau phosphorylation. RNA-seq coupled with Gene Ontology (GO) enrichment analysis implicated <i>L. mucosae</i> WMU007 in modulating oxidative stress in this AD model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and qPCR were performed to identify the specific mechanism by which this probiotic suppresses oxidative stress in the pathogenesis of AD. In addition, we quantified the levels of classical oxidative stress markers, such as superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4). We also examined the expression of cannabinoid receptor type 2 (CB2) and its key downstream regulators in the redox pathway, namely nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), in both animal and cellular models.</p><p><strong>Results: </strong>Our results showed that treatment with <i>L. mucosae</i> WMU007 significantly decreased cognitive impairment, neuronal damage, Aβ deposits, and Tau phosphorylation in APP/PS1 mice. Activation of CB2 was identified as the key mechanism by which <i>L. mucosae</i> WMU007 reduces oxidative stress in AD. In addition, <i>L. mucosae</i> WMU007 reduced oxidative stress and increased the levels of CB2 pathway-related proteins <i>in vivo</i> and <i>in vitro</i>.</p><p><strong>Conclusions: </strong>These results indicate that <i>L. mucosae</i> WMU007 confers neuroprotection in AD by targeting CB2-mediated oxidative pathways, highlighting its therapeutic potential as a novel probiotic intervention.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"48598"},"PeriodicalIF":3.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054850","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":"Research Progress on How Multimodal Signals Regulate Neuronal Mitochondrial Homeostasis to Affect Diabetic Cognitive Impairment.","authors":"Ying Li, Pengwei Zhuang","doi":"10.31083/JIN45956","DOIUrl":"10.31083/JIN45956","url":null,"abstract":"<p><p>Diabetic cognitive impairment (DCI) affects approximately 25%-35% of patients with diabetes and is characterized by progressive cognitive decline. Dysfunction of mitochondria-the energy factories within neurons-is considered a potential pathogenic factor of DCI, involving processes such as oxidative stress, calcium overload, autophagic dysfunction, and genetic mutations, ultimately disrupting normal neuronal function. Maintaining mitochondrial quality and function is critical for neuronal health. Recent studies have shown that there are multiple ways in which cells can communicate signals, such as extracellular vesicles (EVs), tunneling nanotubes and gap junctions, which can repair and replace damaged mitochondria within receptor cells. Notably, EV-mediated mitochondrial transplantation has demonstrated significant potential by transferring healthy mitochondria to impaired neurons and restoring energy metabolism and antioxidant defences, thereby offering novel therapeutic strategies for intervening in DCI progression with valuable clinical translation potential. This review systematically elucidates multimodal signalling strategies targeting mitochondrial homeostasis, with a focused analysis on the role of EV-mediated mitochondrial transplantation in restoring neuronal energy balance, providing a theoretical foundation for the development of innovative DCI interventions.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"45956"},"PeriodicalIF":3.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054858","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":"Digital Twins in Neurology Care: Evidence, Limitations, and a Path Forward.","authors":"Parisa Gazerani","doi":"10.31083/JIN50563","DOIUrl":"10.31083/JIN50563","url":null,"abstract":"<p><p>Digital twins are increasingly promoted in neurology as an advancement beyond conventional artificial intelligence, yet the term is often applied without conceptual or methodological rigor. Strict definitions describe digital twins as dynamically updated, bidirectionally linked models that generate predictive, decision-relevant value, criteria rarely met by current neurological applications. This Opinion critically examines the state of digital twins across major neurological domains, including dementia, multiple sclerosis, Parkinson's disease, epilepsy, stroke, pain, and migraine. We argue that most existing systems are more accurately described as twin-inspired longitudinal decision-support or trial-analytics models rather than true clinical digital twins. While neurology is well-suited to digital twin approaches due to disease heterogeneity, multimodal data, and iterative care pathways, progress is limited by gaps in measurement validity, uncertainty handling, prospective evaluation, and governance. A pragmatic path forward is proposed, emphasizing question-specific, validated neurological digital twins over overgeneralized brain twin narratives, and suggesting that much of the current field is better understood as twin-inspired modeling rather than true clinical digital twin implementation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"50563"},"PeriodicalIF":3.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054840","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":"Single-Cell and Integrative Analyses Uncover Therapeutic Potential of RFX1-Mediated Cuproptosis in PitNETs.","authors":"Shuangjian Yang, Changqin Pu, Congcong Deng, Xuexue Bai, Si Wu, Chenxin Tian, Xueyou Xu, Renzhi Wang, Mengqi Chang, Ming Feng","doi":"10.31083/JIN49669","DOIUrl":"10.31083/JIN49669","url":null,"abstract":"<p><strong>Background: </strong>Pituitary neuroendocrine tumors (PitNETs) have different cell types and levels of growth. We do not fully understand why they grow so much. Cuproptosis is a new way that copper kills cells and it is important in cancer. But, we do not know how it works in PitNETs yet.</p><p><strong>Methods: </strong>We used several methods like bulk and single-cell sequencing with machine learning to investigate cuproptosis in PitNETs. We used Weighted Gene Co-expression Network Analysis (WGCNA) and random forest to find important genes. Then, we did tests in the lab to see how these genes work.</p><p><strong>Results: </strong>Analysis of cuproptosis-related genes (CRGs) revealed significant differences in expression and immune landscapes between invasive and non-invasive PitNETs. We established CRG-based molecular subtypes and a high-performance predictive model for tumor invasiveness. Notably, regulatory factor X1 (RFX1) was identified and validated as a key regulator that suppresses tumor growth and sensitizes cells to cuproptosis. These results highlight the clinical relevance of cuproptosis in PitNET progression and suggest RFX1 as a potential therapeutic target.</p><p><strong>Conclusion: </strong>This study establishes a single-cell-based molecular landscape of PitNETs and uncovers RFX1-mediated cuproptosis as a key suppressive mechanism of tumor progression. These findings not only deepen the understanding of PitNET heterogeneity but also propose RFX1 as a promising therapeutic target for PitNETs.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"49669"},"PeriodicalIF":3.3,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054914","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":"Tea Polyphenols Protect the Blood-Brain Barrier Structure in the Hippocampus of Early Diabetic Mice by Inhibiting the AGEs-RAGE Pathway.","authors":"Zhiyong Xu, Yan Liu, Yan Yu","doi":"10.31083/JIN49065","DOIUrl":"10.31083/JIN49065","url":null,"abstract":"<p><strong>Background: </strong>Diabetic encephalopathy is a prevalent complication of diabetes mellitus, which is primarily characterized by hippocampal injury and blood-brain barrier (BBB) dysfunction. This study investigates the neuroprotective effect of tea polyphenols (TP) on hippocampal tissue in early-stage diabetic mice.</p><p><strong>Methods: </strong>Sixty BALB/c mice were randomly assigned to the control group (C), the diabetes group (T0), and the TP-treated group (T1). After successful model induction, mice in group T1 received TP intragastrically (100 mg/kg/d). Hematoxylin and eosin (H&E), toluidine blue, and Hoechst 33342 staining, combined with polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), were used to assess the effects of TP on hippocampal histology, inflammation and oxidative stress, the advanced glycation end products (AGEs) - Receptor for Advanced Glycation End products (RAGE) pathway, and the expression of key proteins associated with the BBB.</p><p><strong>Results: </strong>The contents of AGEs, RAGE, NF-κB, P-glycoprotein (P38), and oxidative stress factors in group T1 were lower than those in group T0 at 7, 14, and 21 days (<i>p</i> < 0.05). At the same time points, the mRNA expression levels of inflammatory factors in group T1 were lower than those in group T0 (<i>p</i> < 0.05). Moreover, compared with group T0, both P-glycoprotein (P-gp) protein expression and glucose transporters (<i>Glut1</i>) mRNA expression increased in group T1 (<i>p</i> < 0.05). The mRNA expression levels of key BBB-related molecules in group T1 also increased to varying degrees (<i>p</i> < 0.05). Histopathological analysis showed marked improvement in the hippocampal architecture of group T1 compared with group T0. Moreover, the expression levels of P38, NF-κB, <i>IL-6</i>, <i>TNF-α</i>, ROS, and <i>Glut1</i> were significantly or highly significantly positively correlated with RAGE protein levels (<i>p</i> < 0.05 or <i>p</i> < 0.01).</p><p><strong>Conclusions: </strong>TP enhanced BBB structural integrity by inhibiting the AGEs-RAGE pathway, thereby attenuating hippocampal tissue damage.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"49065"},"PeriodicalIF":3.3,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054831","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":"Usefulness of Non-Contrast Electron Density Imaging for the Identification of Brain Tissue Changes in Large Vessel Occlusion Acute Ischemic Stroke.","authors":"Santiago de Erausquin, Andres Polania, Gaston A Rodriguez-Granillo, Pablo Diluca, Carlos Bleise, Pedro Lylyk","doi":"10.31083/JIN50299","DOIUrl":"10.31083/JIN50299","url":null,"abstract":"<p><strong>Background: </strong>Electron density (ED) imaging has shown the ability to discriminate between different soft tissue components in preliminary studies. We hypothesized that ED might improve the identification of brain tissue abnormalities in patients with large vessel occlusion acute ischemic stroke (AIS).</p><p><strong>Methods: </strong>We retrospectively included a series of patients with large vessel occlusion AIS comprising the middle cerebral artery (MCA) territory. All patients underwent non-contrast brain computed tomography (CT) and CT angiography using a dual-layer spectral CT scanner. Using a multiparameter display including conventional CT images (Hounsfield units, HU), ED relative to water (%EDW), and effective atomic number (Zeff), we evaluated the brain tissue territory distal to the occlusion, and the contralateral hemisphere.</p><p><strong>Results: </strong>Twenty-eight patients were included, with a mean age of 75.7 ± 10.9 years. The brain tissue distal to the MCA occlusion showed significant differences compared with the contralateral hemisphere only using conventional CT (25.0 ± 2.7 HU vs. 29.2 ± 2.4 HU, <i>p</i> < 0.0001) and ED imaging (102.2 ± 0.3 %EDW vs. 102.6 ± 0.2 %EDW, <i>p</i> < 0.0001), whereas the Zeff (7.37 ± 0.1 vs. 7.37 ± 0.1, <i>p</i> = 0.36) showed similar values. ED imaging was associated with a significantly higher diagnostic confidence for the identification of abnormal findings, both for the evaluation of the hyperdense MCA (conventional CT 3.46 ± 1.3 vs. ED imaging 4.79 ± 0.4 vs. Zeff imaging 2.07 ± 1.0, <i>p</i> < 0.0001) as well as for the subtended brain parenchyma (conventional CT 3.30 ± 1.3 vs. ED imaging 4.30 ± 0.8 vs. Zeff 1.44 ± 0.6, <i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>In this study, ED imaging enabled a more confident identification of brain tissue changes related to large vessel occlusion AIS compared with conventional CT imaging.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"50299"},"PeriodicalIF":3.3,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054828","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":"The Neuroprotective Role of a Caspase-1 Inhibitor Against Apoptosis via Inhibition of Glial Hyperactivation in a Mouse Model of Epilepsy.","authors":"Hui Cai, Xinran Xu, Xuerui Zhuo, Zhe Liu, Hao Liu, Yiming Sun","doi":"10.31083/JIN49777","DOIUrl":"10.31083/JIN49777","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a central nervous system disorder characterized by abnormal neuronal discharges in the brain. The purpose of this study was to investigate the protective effects of a caspase-1 inhibitor on glial hyperactivation and neuronal apoptosis in epilepsy.</p><p><strong>Methods: </strong>A pilocarpine-induced status epilepticus (SE) mouse model was established. Belnacasan (VX765), a caspase-1 inhibitor, was administered intraperitoneally. ELISA was used to detect inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in peripheral blood. Immunohistochemistry and transmission electron microscopy were used to evaluate glial activation and neuronal damage in the hippocampus. Western blotting was performed to detect caspase-1 and Gasdermin D N-terminal (GSDMD-N) expression. <i>In vitro</i>, primary glial cells were stimulated with lipopolysaccharide (LPS), and the effects of glial conditioned medium on HT22 neuronal apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry.</p><p><strong>Results: </strong><i>In vivo</i> experiments showed that, as epilepsy progressed, the levels of pro-inflammatory cytokines IL-1β and IL-6 in peripheral blood were significantly increased, consistent with findings in patients with epilepsy. At 21 days after epilepsy induction, the numbers of hyperactivated microglia and astrocytes increased significantly and exhibited activation-related features such as organelle swelling, whereas neuronal numbers were markedly reduced and displayed cytological features of apoptosis. VX765 significantly alleviated seizure frequency and severity in epileptic mice and attenuated peripheral blood levels of IL-1β and IL-6, hippocampal caspase-1 activity, glial hyperactivation, and neuronal apoptosis. <i>In vitro</i> experiments demonstrated that glial conditioned medium (CMG) promoted apoptosis of HT22 neurons by regulating Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) expression, whereas VX765 alleviated HT22 neuronal apoptosis by inhibiting the secretion of inflammatory factors from glial cells.</p><p><strong>Conclusions: </strong>These results indicate that inhibiting glial cell hyperactivation and neuroinflammation via caspase-1 inhibition may represent a potential therapeutic strategy for epilepsy.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"49777"},"PeriodicalIF":3.3,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054906","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}