Brain Research最新文献

{"title":"Hardware-based brain tumor classification using graph Laplacian spectral features","authors":"Suman Rekha Dip,&nbsp;Hemant Kumar Meena","doi":"10.1016/j.brainres.2025.150117","DOIUrl":"10.1016/j.brainres.2025.150117","url":null,"abstract":"<div><div>Early and accurate identification of Brain Tumors (BT) is one of the most challenging problems due to the complex, non-Euclidean, and irregular characteristics of brain MRI data. Graph Signal Processing (GSP) offers a robust framework for accurately depicting irregular neighborhood connectivities by modeling brain images as signals on graphs and enables the simultaneous analysis of both the spatial and spectral characteristics of the data. A key aspect of GSP is the construction of an appropriate graph, and thus the performance of the resultant graph-based representation and algorithms depends on the definition of the graph used. However, defining such graphs across diverse application domains is often complex. Ideally, the constructed graph should allow the data to exhibit smoothness or regularity over its topology. To overcome this issue, this study discusses the graph Laplacian, or graph topologies, allowing the brain MRI data to vary smoothly across the graph. We utilize this foundation by employing three forms of the graph Laplacian matrix, such as unnormalized, normalized, and random walk, to extract a discriminative Graph Laplacian Spectral (GLS) feature that accurately represents tumor-induced modifications in brain structure. Experimental evaluations of the Br35H and Kaggle-4600 MRI datasets demonstrate that an unnormalized Laplacian-based GLS feature achieves classification accuracies of 98.33% for Br35H and 98.21% for Kaggle-4600, while maintaining minimal computational cost. These classification results validate the potential of GSP and graph topology learning to improve BT detection by providing a highly effective method of modeling the inherent connectivity of brain tissue. Furthermore, the implementation of the proposed framework on the PYNQ-ZU platform has validated the suitability of our framework for efficient and real-time BT classification.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150117"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780208","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":"A systematic review of the effect of pulse parameters of next-generation TMS devices on corticospinal excitability and neuroplasticity","authors":"Desmond Agboada ,&nbsp;Roman Rethwilm ,&nbsp;Manuel Kuder ,&nbsp;Wolfgang Mack ,&nbsp;Wolfgang Seiberl","doi":"10.1016/j.brainres.2025.150120","DOIUrl":"10.1016/j.brainres.2025.150120","url":null,"abstract":"<div><h3>Background</h3><div>Conventional TMS devices are limited in the number of variations of pulse parameters they produce, which limits the extension of TMS application. Recently, however, successful attempts have been made to introduce next-generation (next-gen) TMS devices with adjustable pulse parameters. Although research using these devices is still in its infancy, a systematic synthesis of the direction of results is valuable to identify the current progress and some limitations of these technologies which can guide further studies in the field.</div></div><div><h3>Objective</h3><div>This review aims to investigate the influence of pulse parameters (width, shape, and current direction) of next-gen TMS devices on corticospinal excitability and the induction of neuroplasticity.</div></div><div><h3>Methods</h3><div>Using the PRISMA method of reporting systematic reviews, we searched major biomedical databases − PubMed (n = 84), Web of Science (n = 141), Scopus (n = 111) and APA PsychInfo (n = 27) for literature, with 21 studies included in this review.</div></div><div><h3>Results</h3><div>Compared to conventional TMS devices, next-generation TMS devices were more efficient in many neurophysiological measurements. For plasticity inducing protocols, both inhibitory and facilitatory protocols showed enhanced respective inhibitory and excitatory after-effects with increasing pulse width. The new near-rectangular pulse shape moreover induced stronger inhibitory after-effects compared to conventional pulses.</div></div><div><h3>Conclusions</h3><div>Next-generation devices expand the parameter space of TMS. Further studies are however needed to explore the full potential of these next-gen devices, especially in non-motor brain regions.</div></div><div><h3>Significance</h3><div>Next-gen TMS devices do hold a promise in the optimization of the neuromodulatory effects of TMS.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150120"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817731","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":"Bridging the gap: Acute amantadine augments the neurorehabilitative efficacy of delayed and abbreviated environmental enrichment in a pediatric traumatic brain injury model","authors":"Andrew M. Victoria ,&nbsp;Haley E. Capeci ,&nbsp;Jade A. Steber ,&nbsp;Hailey M. Donald ,&nbsp;Piper L. Rennerfeldt ,&nbsp;Jeffrey P. Cheng ,&nbsp;Eleni H. Moschonas ,&nbsp;Corina O. Bondi ,&nbsp;Anthony E. Kline","doi":"10.1016/j.brainres.2025.150118","DOIUrl":"10.1016/j.brainres.2025.150118","url":null,"abstract":"<div><div>Environmental enrichment (EE) promotes neurobehavioral recovery after traumatic brain injury (TBI). However, most preclinical studies initiate EE immediately after injury, which contrasts with delayed rehabilitation in the clinic. To better model clinical practice, we delayed the onset of EE and administered amantadine (AMT), which exhibits indirect dopaminergic effects, acutely as a therapeutic bridge. We hypothesized that this temporally sequenced combination therapy would improve neurobehavioral outcomes more than either treatment alone. Post-natal day 21 male rats received a controlled cortical impact or sham surgery and housed in standard (STD) conditions. Beginning 24 h post-surgery, daily intraperitoneal injections of AMT (20 mg/kg) or saline vehicle (VEH; 1 mL/kg) were provided for 7 days (bridge phase). On post-operative day 8, a subset transitioned to abbreviated EE (6 h/day). Vestibulomotor (beam-balance), cognition (spatial learning/memory), and affect (shock probe defensive burying) were assessed on days 8–12, 14–20, and 23, respectively. Hippocampal neuron survival was quantified on day 24. EE, regardless of AMT or VEH treatment, and AMT in STD housing, improved motor and cognitive outcomes versus VEH + STD (<em>p</em> &lt; 0.05). Additionally, AMT + EE outperformed VEH + EE in spatial learning and improved memory retention relative to AMT + STD (<em>p</em> &lt; 0.05). All treatment groups engaged quicker with the shock probe and increased burying behavior compared to VEH + STD. Additionally, the AMT + EE group spent more time burying the probe than the AMT + STD and VEH + EE groups (<em>p</em> &lt; 0.05) and did not differ from SHAM controls (<em>p</em> &gt; 0.05). Both EE groups had more CA3 neurons compared to the STD-housed groups (<em>p</em> &lt; 0.05), while no difference in CA1 neurons was observed among the groups (<em>p</em> &gt; 0.05). Overall, these findings reveal that acute AMT treatment augments the efficacy of delayed and abbreviated EE, particularly in cognitive and affective domains, which support the hypothesis. This temporally staged combination therapy may more accurately model clinical care and lead to greater improvement after TBI.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150118"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803042","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":"GPX4-overexpressing mesenchymal stem cell-derived exosomes ameliorate secondary brain injury after intracerebral hemorrhage by inhibiting neuronal ferroptosis","authors":"Yini Wu,&nbsp;Weifeng Shan,&nbsp;Xin Han,&nbsp;Hong Dai,&nbsp;Ruijun Ma,&nbsp;Jimin Wu","doi":"10.1016/j.brainres.2025.150112","DOIUrl":"10.1016/j.brainres.2025.150112","url":null,"abstract":"<div><div>Closely linked to intracerebral hemorrhage (ICH)-related secondary brain injury, ferroptosis lacks effective treatments, whereas exosomes offer novel neuroprotective potential. This study aimed to investigate the neuroprotective effects and mechanisms of exosomes derived from bone marrow mesenchymal stem cells overexpressing glutathione peroxidase 4 (<em>exo</em>-GPX4) in ICH. In <em>in vitro</em> experiments, <em>exo</em>-GPX4 were constructed and exosomes were extracted using ultracentrifugation, followed by characterization through transmission electron microscopy, nanoparticle tracking analysis, and Western blot. In a hemin-induced HT22 cell injury model, cell viability was detected by CCK-8 assay, apoptosis was analyzed by flow cytometry, and Fe²⁺, MDA, and GSH levels were measured by colorimetric assay, and the expression levels of GPX4, ACSL4, and SLC7A11 proteins were detected by Western blot. <em>In vivo</em> experiments, an ICH rat model was established, and histopathological changes were assessed through neurological function scores, H&amp;E staining, Prussian blue staining, and TUNEL assay. Serum ferroptosis-related indicators were detected using kits, while Western blot and immunofluorescence were employed to examine the expression levels of GPX4, ACSL4, and SLC7A11 proteins and the localization of GPX4, respectively. The results demonstrated that <em>in vitro</em>, <em>exo</em>-GPX4 significantly enhanced cell viability, reduced apoptosis, decreased Fe²⁺ and MDA levels, and increased GSH content. <em>In vivo</em>, <em>exo</em>-GPX4 treatment markedly improved neurological function scores, alleviated cerebral iron deposition and neuronal apoptosis, and modulated serum ferroptosis-related indicators. Mechanistic studies revealed that <em>exo</em>-GPX4 upregulates GPX4 and SLC7A11 protein expression while downregulating ACSL4 expression. In conclusion, <em>exo</em>-GPX4 mitigates secondary brain injury after ICH by inhibiting ferroptosis, revealing a novel therapeutic strategy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150112"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762284","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":"Can thermotherapy mitigate depression? A review of physiological adaptations and clinical evidence","authors":"Øyvind A. Høydal ,&nbsp;Runa R.G. Notøy ,&nbsp;Kjetil L. Høydal","doi":"10.1016/j.brainres.2025.150136","DOIUrl":"10.1016/j.brainres.2025.150136","url":null,"abstract":"<div><div>With a rising prevalence of the major mood disorders, recent years have seen a growing interest in the potential therapeutic value of lifestyle practises such as exercise and thermotherapy. While the beneficial effects of exercise on mental health are now well documented, the potential benefits of thermotherapy<!--> <!-->are less studied. Similarly to exercise, passive heat- and cold exposure may induce physiological responses which counteract the pathophysiological underpinnings of mood disorders such as depression and anxiety. Thus, for prevention or treatment of mood disorders, thermotherapy could complement exercise or be a viable alternative for people with injuries or disability. Here, we first review physiological adaptations to passive heat- or cold treatment in the context of hypotheses for the<!--> <!-->pathogenesis of depression. Next, we review clinical interventions investigating effects of passive heat- or cold treatment on depressive disorder, before ending with a discussion of future directions.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150136"},"PeriodicalIF":2.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854423","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":"Effects of anodal transcranial direct current stimulation over the right posterior parietal cortex on Simon task and flanker task performance","authors":"Sho Kojima ,&nbsp;Kako Tanabe ,&nbsp;Mitsuki Todoroki ,&nbsp;Hideaki Onishi","doi":"10.1016/j.brainres.2025.150100","DOIUrl":"10.1016/j.brainres.2025.150100","url":null,"abstract":"<div><h3>Introduction</h3><div>Stimulus-response compatibility (SRC) tasks test cognitive judgment by requiring discrimination between relevant and irrelevant information. This study explored the effects of anodal transcranial direct current stimulation (tDCS) over the posterior parietal cortex (PPC) on performance in the Simon and Flanker tasks.</div></div><div><h3>Methods</h3><div>Fifteen healthy, right-handed adults (age: 21.3 ± 0.6 years) participated in the study, completing the Simon and Flanker tasks before and after active and sham tDCS conditions in a crossover design. Sessions were randomized with a 5-day interval between them. Anodal tDCS (1 mA) was applied to the right PPC for 15 min, with sham stimulation lasting 30 s. Task performance was evaluated based on reaction time and accuracy pre- and post-stimulation. Statistical analyses were conducted using nonparametric tests.</div></div><div><h3>Results</h3><div>For congruent Simon task trials, reaction times significantly decreased post-intervention for active and sham tDCS, with no change for incongruent trials. The SRC effect significantly decreased following active tDCS but remained unchanged with sham stimulation. For the Flanker task, no significant differences in SRC effects were observed pre- and post-intervention.</div></div><div><h3>Conclusions</h3><div>Anodal tDCS over the right PPC improved Simon task performance by reducing the SRC effect. No significant changes were observed in the Flanker task, suggesting that the PPC’s role in interference control may be specific to spatial compatibility effects, as seen in the Simon task.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150100"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699563","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":"Differential neural activity and connectivity patterns in rats with and without noise-induced tinnitus","authors":"Nian Li ,&nbsp;Liqin Zhang ,&nbsp;Xu Tian ,&nbsp;Yang Zhao ,&nbsp;Guodong Feng ,&nbsp;Zhiqiang Gao","doi":"10.1016/j.brainres.2025.150106","DOIUrl":"10.1016/j.brainres.2025.150106","url":null,"abstract":"<div><h3>Introduction</h3><div>This study investigates the role of central nervous system networks outside the auditory system in the development of tinnitus.</div></div><div><h3>Methods</h3><div>Twenty Sprague-Dawley rats were exposed to 96 dB SPL narrowband noise (right ear, 1 h); nine unexposed rats served as controls. Tinnitus presence was evaluated through gap prepulse inhibition of acoustic startle (GPIAS-PPI), which divided the exposed rats into tinnitus (ET, n = 8) and non-tinnitus (ENT, n = 12) groups. The auditory brainstem response (ABR) was utilized to evaluate hearing thresholds and wave I parameters. Resting-state fMRI (rs-fMRI) revealed significant increases/decreases in resting-state indices, including the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity.</div></div><div><h3>Results</h3><div>ABR exhibited no intergroup threshold differences. Post-exposure, ET and ENT groups exhibited a decrease in click-evoked wave I amplitude compared to pre-exposure levels, along with an increase in 8 kHz wave I amplitude compared to controls. Rs-fMRI revealed that the ET group had increased ALFF in the entorhinal cortex, amygdala, hippocampus, and superior colliculus, and decreased ALFF in the cingulate and prelimbic cortices. The ENT group showed increased cerebellar activity and decreased basal forebrain activity. ReHo was elevated in the ET group’s entorhinal/amygdala and reduced in the cingulate cortex, whereas the ENT group showed reduced basal forebrain/striatum ReHo. ET weakened amygdala-sensory connections and ENT enhanced basal forebrain-cingulate/sensory connectivity.</div></div><div><h3>Conclusion</h3><div>Noise-exposed rats with/without tinnitus exhibit distinct neural activity/connectivity patterns, supporting a noise-cancellation gating mechanism. Compensatory prelimbic cortex/striatum connectivity may prevent tinnitus in the ENT group. Further research should target noise elimination pathways and the hippocampal/entorhinal roles in “abnormal auditory memory.”</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150106"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762305","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 preference for ammonium may be attributed to a hyperpolarized membrane potential via TWIK-1 channels","authors":"Lanying Pan ,&nbsp;Brendan Zhu ,&nbsp;Simon L Vu ,&nbsp;Antony Stalin ,&nbsp;Ashley Winters ,&nbsp;Qizhi Gong ,&nbsp;Yuan Chen","doi":"10.1016/j.brainres.2025.150109","DOIUrl":"10.1016/j.brainres.2025.150109","url":null,"abstract":"<div><div>Urine, which contains ammonium, transmits crucial signals among animals. However, the mechanism underlying signal transmission remains unknown. In our study, we observed that there are significant differences in olfactory preference depending on ammonium concentrations of 0.0004 %, 0.004 %, and 0.04 % between TWIK-1 gene knockout (TWIK-1^−/−) and wild-type (WT) mice (p &lt; 0.05, n = 6), although there is no significant preference difference between the 4 % concentration groups. These results are consistent with calcium imaging data, which showed an increase in calcium fluorescence only in the olfactory epithelium (OE) of TWIK-1^−/− mice at 4 and 400 µM NH₄⁺ concentrations, but in both groups at 40 mM NH₄⁺. The electrophysiological results indicate an increase in the amplitudes of the inward current that hyperpolarizes the membrane potential at 400 µM NH₄⁺, while it depolarizes the membrane potential at higher NH₄⁺ concentrations. These findings suggest a potential mechanism by which ammonium hyperpolarizes the membrane potential via TWIK-1 channels at low concentrations, making the OE cells more difficult to activate and resulting in the differences in olfactory preference between the two groups.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150109"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740586","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":"Tirzepatide reverses hypothalamic inflammation, cellular stress, and neuropeptide imbalance in metabolic–menopausal dysfunction","authors":"Thatiany Souza Marinho,&nbsp;Julie Oliveira A. Bittencourt,&nbsp;Marcia Barbosa Aguila,&nbsp;Carlos A. Mandarim-de-Lacerda","doi":"10.1016/j.brainres.2025.150113","DOIUrl":"10.1016/j.brainres.2025.150113","url":null,"abstract":"<div><div>Obesity, diabetes, and menopause impair hypothalamic regulation of energy balance by inducing inflammation, cellular stress, and disruption of neuropeptide signaling. In a female mouse model combining these conditions, we investigated whether tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, restores hypothalamic homeostasis by integrating gene and protein expression analyses. Ovariectomized and sham-operated mice were fed either a control or high-fat, high-sucrose diet and then treated with tirzepatide for four weeks. Metabolic and hormonal stress induced robust activation of inflammatory pathways, elevated cytokine and chemokine expression, marked endoplasmic reticulum stress, and enhanced microglial reactivity, accompanied by a shift toward appetite-stimulating neuropeptides and reduced expression of appetite-suppressing neuropeptides. Tirzepatide produced broad hypothalamic benefits, markedly suppressing inflammatory and stress-related markers, reprogramming microglia toward an anti-inflammatory phenotype, and restoring neuropeptide balance by reducing agouti-related peptide and neuropeptide Y while increasing proopiomelanocortin and melanocortin 4 receptor expression. Treatment also lowered suppressor of cytokine signaling 3 and normalized doublecortin expression, indicating enhanced neuronal plasticity and recovery of hypothalamic circuitry. Multivariate analysis demonstrated that tirzepatide shifted the overall hypothalamic molecular profile of obese-diabetic and ovariectomized mice to that of control groups, highlighting coordinated improvement across inflammatory, glial, and neuropeptidergic pathways. In conclusion, these findings show that tirzepatide exerts potent and broad central nervous system actions capable of counteracting hypothalamic inflammation, cellular stress, microglial activation, and neuropeptide dysregulation under severe metabolic–hormonal challenge, supporting its therapeutic potential to restore hypothalamic integrity and metabolic control in obesity and diabetes during menopause.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150113"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773412","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":"Cross-Disease myeloid remodeling along the GMP–TAM axis predicts immunotherapy response in glioma","authors":"Yuanyuan Zhang ,&nbsp;Xin Liu ,&nbsp;Shi Hua","doi":"10.1016/j.brainres.2025.150083","DOIUrl":"10.1016/j.brainres.2025.150083","url":null,"abstract":"<div><h3>Backgrounds</h3><div> <!-->Immune checkpoint inhibitor-induced colitis (CICs) represents a state of systemic immune activation and is paradoxically associated with superior anti-tumor responses. This study has been designed to explore gene signatures derived from CICs that could identify the key immunological drivers, and predict sensitivity of immunotherapy in immunologically cold tumors e.g. glioma. <strong>Methods:<!--> </strong>We integrated bulk, single-cell, and spatial transcriptomic data from CICs and glioma cohorts. Cross-disease analysis have been performed to identify an immunotherapy-responsive granulocyte-monocyte progenitor (IR-GMP) signature. Risk score (RS) model has been constructed through LASSO regression, and have been validated for its potential prognostic as well as predictive values. <strong>Results:<!--> </strong>We have identified 112 IR-GMP genes enriched in pathways that may cause myeloid immunosuppression. A four-gene RS model (RAC2, LAPTM5, HCLS1, CD74) has been developed, and glioma patients have been divided into high- and low-risk groups based on the model. RS is an independent prognostic factor, and demonstrated to exhibit superior accuracy for predicting survival when combining with clinical variables. High-RS tumors exhibited immunosuppressive TME characterized by M2 macrophage enrichment, SPP1-signaling hyperactivation, and an immune-tolerant genomic landscape (C4 subtype). Crucially, the high-RS group showed significantly higher immunophenoscores under PD-1 and combined PD-1/CTLA-4 blockade, indicating potential sensitivity to immunotherapy, and distinct chemotherapy susceptibility. Single-cell and spatial transcriptomic results confirmed the lineage specificity and regional colocalization of RS genes with M2 macrophages. <strong>Conclusions:</strong> <!-->Our cross-disease analysis unveils a conserved GMP–TAM myeloid remodeling axis in glioma. The derived RS model may serve as a powerful marker for predicting prognosis, and also for predicting the benefits derived from immunotherapy, offering a novel tool for precision immunotherapy in glioma.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150083"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660102","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}