Brain Research Bulletin最新文献

{"title":"Altered functional topology related to the development of wearing-off in Parkinson’s disease","authors":"Ting Gao,&nbsp;Cheng Zhou,&nbsp;Tao Guo,&nbsp;Jun Tian,&nbsp;Xiaojun Guan,&nbsp;Jingjing Wu,&nbsp;Xiaojun Xu,&nbsp;Minming Zhang,&nbsp;Jiali Pu,&nbsp;Baorong Zhang","doi":"10.1016/j.brainresbull.2026.112136","DOIUrl":"10.1016/j.brainresbull.2026.112136","url":null,"abstract":"<div><h3>Introduction</h3><div>Wearing-off (WO) is the most common medicine-related complication that develops in later stage of Parkinson’s disease (PD), whereas the underlying mechanism still remains unknown. Here, we aimed to decipher the mechanism underlying the WO in PD patients.</div></div><div><h3>Methods</h3><div>Twenty-six PDWO (PD with WO), 26 PDnW (PD without WO) and 34 healthy controls were included and functional and structural magnetic resonance imaging (MRI) were employed. Functional network was constructed based on the matrix of each subject’s functional images and attributes of functional topology (e.g., global and local metrics) were calculated. Intergroup differences in white matter and grey matter were compared to potentially explore the structural abnormalities. Partial correlation analysis was performed to demonstrate the relationships between the altered imaging findings and clinical variables.</div></div><div><h3>Results</h3><div>Wearing-off in PD patients was independently associated with levodopa equivalent daily dose (LEDD) /weight. Functional degree centrality (DC) having negative correlation with WO severity was significantly decreased in supramarginal gyrus in PDWO. Functional DC in precentral gyrus was significantly lower in PDnW compared with healthy controls, which was correlated with dopaminergic medication profiles. No apparent evidence about structural abnormality was found in PDWO and PDnW patients.</div></div><div><h3>Conclusions</h3><div>The occurrence of wearing-off in PD patients was independently associated with LEDD/weight. The functional disruption in supramarginal gyrus might reflect the development of wearing-off, and we speculated the attenuation of levodopa related plasticity in precentral gyrus had an association with the susceptibility of wearing-off in PD patients. Further research are needed to validate and extend these preliminary findings.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"245 ","pages":"Article 112136"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosylation in neurological disorders: Mechanisms, crosstalk, and therapeutic implications","authors":"Wenbo Wu,&nbsp;Wanyu Wang,&nbsp;Lintao Xu,&nbsp;Ying Yao,&nbsp;Xinyue Zhao,&nbsp;Jinjie Zhong,&nbsp;Jue Hu,&nbsp;Linlin Wang,&nbsp;Yongjian Zhu,&nbsp;Jingyu Wang","doi":"10.1016/j.brainresbull.2026.112144","DOIUrl":"10.1016/j.brainresbull.2026.112144","url":null,"abstract":"<div><div>Neurological disorders pose a major global health challenge for complicated pathogenesis and a lack of effective curative treatments. As a post-translational modification, glycosylation has emerged as a multifunctional regulator in the nervous system, influencing key processes including receptor activation, cell adhesion, and immune surveillance. Its dysfunction is increasingly recognized as a shared mechanism across various neurological disorders. This review synthesizes the molecular mechanisms of glycosylation within a novel framework of four neurological disorder categories: neurodevelopmental disorders, proteostasis disorders, neuroimmunological disorders, and acute nerve injuries. Furthermore, we advance the concept of glycosylation as an integrator of mechanistic crosstalk and demonstrate its pivotal role in bridging and amplifying intertwined pathological cascades. This integrative perspective aims to reframe the understanding of disease pathogenesis and inspire innovative diagnostic paradigms and therapeutic strategies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"245 ","pages":"Article 112144"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural connectivity patterns associated with high-altitude residence duration: An exploratory cross-validated multimodal MRI study","authors":"Fang Guan,&nbsp;Weiwei Xie,&nbsp;Fei Wang,&nbsp;Hailin Ma,&nbsp;Ying Li,&nbsp;Yongfa Zhang,&nbsp;Kaiping Peng","doi":"10.1016/j.brainresbull.2026.112127","DOIUrl":"10.1016/j.brainresbull.2026.112127","url":null,"abstract":"<div><div>Living at high altitudes (HA) poses challenges to the brain due to hypobaric hypoxia. However, most neuroimaging studies have focused on group-level comparisons, leaving the brain features associated with individual differences in HA residence duration incompletely characterized. We therefore used a data-driven, individualized, multimodal machine learning framework for exploratory cross-validated association analysis to estimate individuals’ HA residence duration after adjustment for age and gender. The analysis included 217 healthy migrants at HA and incorporated whole-brain anatomical morphometry, structural connectivity (SC), and functional connectivity (FC). Resting-state FC showed the highest estimate–target correlation among the unimodal models (<em>r</em> = 0.34, permutation <em>p</em> = 0.01, out-of-sample predictive <em>R²</em> = −0.15, MAE = 41.04 months, RMSE = 52.39 months). Combining FC and SC produced a numerically higher <em>r</em> and lower MAE and RMSE (<em>r</em> = 0.36, permutation <em>p</em> = 0.01, out-of-sample predictive <em>R²</em> = 0.00, MAE = 38.37 months, RMSE = 48.86 months) than FC alone, but the difference in correlation was not statistically significant. The FC model thus showed a statistically significant but modest cross-validated association with the residualized target, but its accuracy was insufficient to support clinical prediction or monitoring of HA residence duration. Meanwhile, FC within the somatomotor network (SMN) showed a positive contribution to model estimation, while FC between the SMN and the default mode network (DMN) showed a negative contribution. Positive contributions were observed for SC between the DMN and the frontoparietal network and for FC between the DMN and the dorsal attention network. SC between the thalamus and the posterior superior temporal sulcus (pSTS) showed a positive contribution to model estimation. Whether these residence-duration–associated connectivity patterns reflect within-person changes over time requires longitudinal investigation. As no behavioral validation was performed in this study, the functional significance of these connectivity patterns remains to be determined.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"245 ","pages":"Article 112127"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontal midline theta reduction during attentional reconfiguration links local cortical dynamics to network-level connectivity changes","authors":"Tomohiro Ohgomori,&nbsp;Keigo Shiraiwa,&nbsp;Yasuo Naito,&nbsp;Ryouhei Ishii,&nbsp;Masatoshi Takeda","doi":"10.1016/j.brainresbull.2026.112139","DOIUrl":"10.1016/j.brainresbull.2026.112139","url":null,"abstract":"<div><div>Attentional reconfiguration during transitions between task contexts induces a transient reduction of frontal midline theta (Fmθ), a well-established neural marker of focused attention. However, it remains unclear whether this transient reduction reflects changes in local cortical activity associated with specific visual information processing or a more general reorganization of network-level connectivity. Thirty-six healthy young adults performed a rule-switching 2-back task that required attentional shifts between color-based and position-based processing. Electroencephalography was recorded using a 19-channel system and we compared changes in power spectral density, current source density, and lagged linear functional connectivity between epochs immediately before and after attentional reconfiguration using exact low-resolution electromagnetic tomography technique. Statistical analyses were conducted using permutation-based non-parametric methods. Transient reductions in Fmθ power and the number of Fmθ-positive epochs were consistently observed across both rule-switching patterns. In contrast, α band activity showed condition-dependent spatial modulation: parietal α suppression emerged selectively during shifts toward spatial processing, whereas occipital α suppression was observed during shifts toward color processing. Moreover, Fmθ reduction was significantly associated with parietal (but not occipital) α suppression. Connectivity analysis revealed robust increases in long-range θ-band coordination following attentional reconfiguration across conditions. These findings suggest that transient Fmθ reduction during attentional reconfiguration reflects at least two partially dissociable processes: θ-band connectivity changes consistent with network-level reconfiguration associated with attentional reconfiguration in general, and local cortical dynamics selectively related to spatial information processing.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"245 ","pages":"Article 112139"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PI3K/AKT signaling contributes to prenatal nicotine exposure-induced developmental impairment of the pontomedullary respiratory network in neonatal rats","authors":"Yu Du,&nbsp;Simin Liang,&nbsp;Min Bian,&nbsp;Yi Wang,&nbsp;Zhengmin Xu,&nbsp;Qian Wang,&nbsp;Faping Tu,&nbsp;Ji Wang","doi":"10.1016/j.brainresbull.2026.112128","DOIUrl":"10.1016/j.brainresbull.2026.112128","url":null,"abstract":"<div><div>Prenatal nicotine exposure (PNE) disrupts the development of the pontomedullary respiratory network and increases susceptibility to respiratory dysfunction after birth. However, the role of PI3K/AKT signaling in PNE-induced impairment of neuronal development within the pontomedullary respiratory network remains unclear. In this study, a rat model of PNE was established to investigate neuronal development, apoptosis, microglial activation, and PI3K/AKT signaling within respiratory-related nuclei of the pontomedullary network in neonatal rats on postnatal day 2. PNE induced neuronal morphological abnormalities and reduced NeuN-positive neuronal populations in the VIIn/pFRG, XIIn, and NA/pre-BötC regions. These changes were accompanied by increased TUNEL-positive cells, elevated caspase-3 and caspase-9 expression, enhanced microglial activation as indicated by increased Iba-1-positive cells, and increased PIK3CA expression and the p-AKT1/AKT1 ratio. Pharmacological inhibition of PI3K/AKT signaling with wortmannin partially attenuated neuronal development impairment, apoptosis, and microglial activation. PNE was also associated with reduced neonatal body weight and length. These findings provide pharmacological evidence that dysregulated PI3K/AKT signaling contributes to PNE-induced developmental impairment of the pontomedullary respiratory network, potentially through processes involving neuronal apoptosis and microglial activation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"245 ","pages":"Article 112128"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized brain-based anesthetic-state detection with portable fNIRS and AI","authors":"Cristian Minoccheri,&nbsp;Pangyu Joo,&nbsp;Xiao-Su Hu,&nbsp;Hafsa Affendi,&nbsp;Fadi Elayyan,&nbsp;Angeline Harville,&nbsp;Neville J. McDonald,&nbsp;Tatiana Botero,&nbsp;Alexandre F. DaSilva","doi":"10.1016/j.brainresbull.2026.112129","DOIUrl":"10.1016/j.brainresbull.2026.112129","url":null,"abstract":"<div><div>Portable functional near-infrared spectroscopy (fNIRS) may support brain-based monitoring around local anesthesia, but between-patient variability and patient-overlapping validation can limit generalization. We examined affected-tooth classification before versus after anesthesia, exploratory Pre-session affected-versus-healthy classification using both resting-state and held-out healthy-tooth reference schemes, and validation inflation. We analyzed fNIRS data from 25 patients during percussion before (\"Pre\") and after (\"Post\") anesthesia. The primary cohort comprised 13 patients with complete pain abolition; 156 affected-tooth epochs were classified using Pre-session healthy-tooth responses as patient-specific references. Leave-one-subject-out (LOSO) validation tested each patient using models trained on the others. A random forest using a fixed, data-informed three-feature oxyhemoglobin (HbO) panel achieved mean area under the receiver operating characteristic curve (AUC) = 0.752 (95% confidence interval [CI], 0.624–0.865; one-sided exact conditional p = 0.0057). Fold-nested selection yielded AUC = 0.740. Referencing improved estimates for two of four classifiers. In Pre-session analyses, resting-state and split-half referencing increased affected-versus-healthy AUC from matched raw values of 0.513 and 0.524–0.731 (12 patients) and 0.782 (21 patients); both gains survived eight-comparison adjustment. Because tooth blocks followed a fixed order, these pain-related estimates may include block-position effects. Across 32 feature-based configurations, pooled-epoch cross-validation exceeded LOSO by a mean of 0.159 AUC (95% CI 0.078–0.252); inflation was also positive in all three aligned waveform models. These results support proof-of-concept held-out-patient classification of pain-related affected-tooth responses before versus after anesthesia, exploratory referenced affected-versus-healthy classification before anesthesia, and patient-disjoint validation for estimating performance in new patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"245 ","pages":"Article 112129"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Niosome-encapsulated hesperidin accelerates antioxidant defense and TRPM2 protein expression to restore cognitive function in a rat model of depression","authors":"Mahsa Otarkhani,&nbsp;Homeira Hatami,&nbsp;Yousef panahi,&nbsp;Sama Yavari,&nbsp;Somayeh Hatami,&nbsp;Maryam Azami,&nbsp;Ali Eslami","doi":"10.1016/j.brainresbull.2026.112137","DOIUrl":"10.1016/j.brainresbull.2026.112137","url":null,"abstract":"<div><h3>Aims</h3><div>Hesperidin is a potent antioxidant; however, its therapeutic efficacy is hindered by limited bioavailability. Furthermore, the role of TRPM2 in oxidative stress-induced depression remains to be elucidated. This study investigated the therapeutic potential of niosomal hesperidin in a reserpine-induced depression rat model, focusing on learning and memory performance, oxidative stress markers, and TRPM2 protein expression.</div></div><div><h3>Methods and materials</h3><div>36 rats were randomly divided into six groups: Control, depression (Reserpine), free hesperidin, Niosomal hesperidin, treatment with hesperidin, and treatment with niosomal hesperidin. Reserpine 0.5 mg/kg was administered intraperitoneally for 14 days. Then, rats received hesperidin (20 mg/kg, 14 days) and niosomal hesperidin (20 mg/kg, 7 days). The novel object recognition and shuttle box tests were performed. Finally, glutathione peroxidase levels, serum superoxide dismutase, and western blotting for TRPM2 protein expression were measured.</div></div><div><h3>Results</h3><div>SOD activity and GPX levels increased in the reserpine-induced rats treated with hesperidin and niosome hesperidin (P &lt; 0.05). TRPM2 protein expression decreased in niosome-hesperidin-treated groups compared to the depression group (P &lt; 0.0001). The discrimination index increased in the reserpine-induced rats treated with niosome hesperidin compared to the depression group (P &lt; 0.001). The total time spent in the white box increased in the shuttle box in the reserpine-induced rats treated with niosome hesperidin compared to the control group (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Niosomal encapsulation accelerates cognitive recovery and modulates antioxidant capacity and TRPM2 protein expression. Thus, niosomal hesperidin represents a promising nanocarrier strategy for managing depression-related cognitive dysfunction.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"245 ","pages":"Article 112137"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Needle-knife attenuates excessive autophagy and ferroptosis in post-stroke spastic hemiplegia: Association with SDC1/NRF2/SLC7A11/GPX4 pathway.","authors":"Yinyu Wang, Qingyan Zhou, Shuo Yang, Minghui Liu","doi":"10.1016/j.brainresbull.2026.112167","DOIUrl":"10.1016/j.brainresbull.2026.112167","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to explore the molecular mechanism of needle-knife in inhibiting ferroptosis and excessive activation of autophagy, reducing nerve injury and improving motor function in post-stroke spastic hemiplegia (PSSH) rats.</p><p><strong>Methods: </strong>A rat model of PSSH was established using middle cerebral artery occlusion (MCAO). Neurological function and motor performance were evaluated using modified Ashworth Scale (mASS), Modified Ashworth Scale (MAS) and balance beam test. TTC staining, Nissl staining and transmission electron microscopy were used to detect the cerebral infarction area and neuronal injury. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), glutathione (GSH) and ferrous ion (Fe²⁺) were measured by ELISA. Protein expressions of SDC1, nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), GPX4 and autophagy-related proteins (LC3, p62, Beclin1) were determined by immunohistochemistry (IHC) or Western blotting (WB).</p><p><strong>Results: </strong>Compared with the sham group, the cerebral infarction area of rats in MCAO and Erastin groups increased, the neuronal damage was obvious and the mitochondrial structure was disordered. The levels of ROS, MDA and Fe²⁺ in the infarct area were significantly increased (P < 0.05), and the levels of GSH and GPX4 were decreased (P < 0.05). At the same time, the expressions of SDC1, NRF2, SLC7A11 and GPX4 in the infarction area were decreased (P < 0.05), the autophagy-related proteins LC3II/I and Beclin1 were increased (P < 0.05), and P62 was decreased (P < 0.05). Compared with the MCAO group, the needle knife treatment could improve the nerve damage in PSSH rats, restore their motor functions, and rescue the aforementioned molecular levels (P < 0.05). Compared with the needle knife group, the ferroptosis activator (Erastin), NRF2 inhibitor (ML385), and autophagy activator (rapamycin) significantly reversed the therapeutic effect of the needle knife (P < 0.05).</p><p><strong>Conclusions: </strong>Needle-knife alleviates ferroptosis and inhibits excessive autophagy in PSSH rats, and the underlying mechanism may be potentially related to the upregulation of SDC1 and the NRF2/SLC7A11/GPX4 pathway.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"112167"},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffusion MRI Assessment of White Matter Microstructure and Free-Water Fraction in Drug-Naïve Children with SeLECTS.","authors":"Xiaoling Zhou, Yuwei Chen, Yu Luo, Yangying Kuang, Chen Deng, Hua Lai","doi":"10.1016/j.brainresbull.2026.112163","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.112163","url":null,"abstract":"<p><strong>Background: </strong>Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a common childhood-onset focal epilepsy syndrome. Although seizures are typically self-limited, some children may show neurodevelopmental or cognitive vulnerability. Diffusion MRI may provide insight into white matter alterations in SeLECTS. Objective To evaluate white matter diffusion differences in newly diagnosed, drug-naïve children with SeLECTS using tract-based spatial statistics (TBSS) and white matter free-water fraction (FW-WM), and to explore within-patient associations with selected seizure-related and cognitive variables. Methods Fifty-three newly diagnosed, drug-naïve children with SeLECTS and 53 healthy controls with a similar age and sex distribution were prospectively enrolled in this cross-sectional case-control study. Diffusion MRI was acquired at 3.0T, and white matter diffusion differences were assessed using TBSS and FW-WM analyses. Voxelwise between-group differences in fractional anisotropy (FA) were tested with age and sex as covariates and corrected using threshold-free cluster enhancement-based family-wise error correction. FW-WM was compared between groups using age- and sex-adjusted general linear models, with additional adjustment for years of education in a sensitivity analysis. Exploratory within-patient associations between imaging measures and selected clinical or cognitive variables were assessed using partial Spearman correlations with false-discovery-rate correction. Results Children with SeLECTS showed lower FA than healthy controls in multiple TBSS-defined white matter regions after correction for multiple comparisons, mainly involving commissural, projection, and association pathways. No between-group differences in mean, axial, or radial diffusivity survived correction for multiple comparisons. FW-WM was higher in the SeLECTS group after adjustment for age and sex (adjusted mean difference = 0.0085; 95% CI, 0.0023 to 0.0147; P = 0.008), with similar results after additional adjustment for education. In exploratory cluster-level analyses, mean FA in a left-sided cluster involving the posterior internal capsule, posterior thalamic radiation, and sagittal stratum was inversely associated with disease duration after FDR correction (r = -0.413; P = 0.003; q = 0.010). No imaging-cognition or within-patient FW-WM-FA association survived FDR correction. Conclusions Newly diagnosed, drug-naïve children with SeLECTS showed white matter diffusion differences, including lower FA in distributed TBSS-defined regions and higher FW-WM. These findings support diffusion MRI-based characterization of white matter alterations at diagnosis, before antiseizure treatment. Longitudinal studies are needed to clarify their clinical and developmental relevance.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"112163"},"PeriodicalIF":4.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOTCH1 and ADORA3 define a novel transdifferentiation-related prognostic index for prognostic stratification in glioblastoma by integrating clinical factors.","authors":"Zong-Qing Zheng, Yi-Xiao Li, Yong-Xiang Zhang, Chen-Yang Huang, Chen-Xi Li, Jia-Liang Lin, Hao-Jin Yu, Hong-Zhi Gao","doi":"10.1016/j.brainresbull.2026.112166","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.112166","url":null,"abstract":"<p><strong>Background/objectives: </strong>Glioblastoma (GBM) exhibits aggressive progression and poor prognosis, partly driven by glioma stem cell-endothelial transdifferentiation (GSC-ET), an alternative vascularization mechanism associated with therapeutic resistance. However, robust prognostic models based on transdifferentiation-related genes remain lacking. This study aimed to identify key GSC-ET-associated genes and develop a personalized prognostic framework integrating molecular and clinical factors.</p><p><strong>Methods: </strong>Transcriptomic and clinical data from patients with primary IDH-wildtype GBM were obtained from CGGA, TCGA, Gravendeel (GSE16011), and Murat (GSE7696) cohorts. Survival analyses and Cox regression were performed to identify prognostic transdifferentiation-related genes. A glioblastoma transdifferentiation (GTN) index was established based on candidate genes and integrated with clinical variables to construct a prognostic risk model. External validation, immune infiltration analysis, and functional assays were conducted.</p><p><strong>Results: </strong>Among 12 transdifferentiation-related genes, NOTCH1 and ADORA3 were identified as independent adverse prognostic factors in GBM. A GTN index derived from these genes effectively stratified patient survival and was validated across external cohorts. Integration of the GTN index with age and chemotherapy status generated a risk model with favorable predictive performance and clinical utility. Immune analyses revealed distinct associations between NOTCH1/ADORA3 expression and immune cell infiltration. Functional experiments demonstrated that silencing either gene suppressed tube formation, reduced CD31 expression, and impaired LDL uptake in glioma cells.</p><p><strong>Conclusions: </strong>NOTCH1 and ADORA3 are associated with GBM prognosis, and their silencing reduces transdifferentiation-related endothelial-like phenotypes, supporting their inclusion in an integrated prognostic framework.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"112166"},"PeriodicalIF":4.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}