Brain Research Bulletin最新文献

{"title":"Characterizing White Matter and Structural Brain Network Alterations in Children with Growth Hormone Deficiency Using Diffusion Tensor Imaging.","authors":"Xuewen Wang, Hui Tan, Donglong Lin, Gengbiao Zhang, Kongqing Li, Jin Wang, Hongyi Zheng, Hongwu Wang, Wenbin Zheng","doi":"10.1016/j.brainresbull.2026.112197","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.112197","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize white matter microstructure and structural brain network topology in children with growth hormone deficiency (GHD) using diffusion tensor imaging and explore their associations with clinical indicators.</p><p><strong>Methods: </strong>A total of 77 short-stature children (GHD = 50, idiopathic short stature [ISS] = 27) and 40 healthy controls (HC) underwent 3D-T1WI and DTI. Nineteen participants were excluded due to poor data quality (10 in the GHD group, 4 in the ISS group, and 5 in the HC group), yielding a final analytical cohort of 40 children with GHD, 23 with ISS, and 35 healthy controls. Tract-Based Spatial Statistics and graph-theoretical analysis were applied to characterize white matter microstructure and network topological properties. Clinical metrics including bone age and pituitary volume were collected.</p><p><strong>Results: </strong>Children with GHD showed reduced fractional anisotropy together with elevated mean and radial diffusivity relative to controls. Children with ISS showed elevated mean and radial diffusivity without a reduction in fractional anisotropy, and their diffusivity elevations exceeded those observed in the GHD group. Graph-theoretical analysis revealed that the GHD group had significantly higher global efficiency and lower characteristic path length than the HC group, as well as lower clustering coefficient than the ISS group. Rich-club findings were contingent on both the method used to define core nodes and the connection retention thresholds applied to backbone networks. Nodal analysis identified significantly higher betweenness centrality of the left insula in ISS compared with both the GHD and HC groups. Significant associations were observed between white matter microstructural properties, network connectivity, and clinical variables, including age, bone age, and bone age delay.</p><p><strong>Conclusion: </strong>Children with GHD exhibit altered white matter microstructure and global organization of the structural brain network, which differed from the pattern observed in ISS, and these imaging measures were associated with age, bone age, and bone age delay; given the cross-sectional design, causal inference remains unwarranted.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"112197"},"PeriodicalIF":4.5,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149369896","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":"Cognitive impairment in age-related hearing loss: linking brain structure, glymphatic function, and molecular mechanisms.","authors":"Chunhua Xing, Yinjuan Du, Yuting Xia, Shuo Li, Xiaomin Xu, Richard Salvi, Guanghao Chen, Yu-Chen Chen, Yong Xiao","doi":"10.1016/j.brainresbull.2026.112207","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.112207","url":null,"abstract":"<p><p>The neurobiological mechanisms of cognitive impairment in age-related hearing loss (ARHL) remain unclear. This study examined multi-level neural mechanisms from macroscale gray matter (GM) structure, microscale glymphatic function, and imaging transcriptomics. Sixty-nine ARHL patients and 76 controls underwent multimodal MRI and neuropsychological assessments. Glymphatic function was assessed via DTI-ALPS index and choroid plexus volume (CPV). Transcriptomic analysis using Allen Human Brain Atlas identified molecular pathways and key genes linked to GM atrophy. ARHL patients showed GM atrophy in right amygdala, left inferior frontal gyrus, and orbitofrontal cortex (OFC), but increased volume in left cerebellum. They also exhibited reduced ALPS index and enlarged CPV. Mediation analysis showed a significant indirect effect of glymphatic function on visual memory via right amygdala volume. Transcriptomics revealed enrichment in axonogenesis, energy metabolism, and protein ubiquitination, with key drivers including SMURF1 and GAD1. ARHL-related cognitive decline may follow a cascade from sensory deprivation to glymphatic dysfunction, involving energy metabolism, protein homeostasis, and axonal remodeling, ultimately leading to degenerative atrophy and compensatory adaptation in specific brain networks.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"112207"},"PeriodicalIF":4.5,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149369897","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":"Glutamatergic Dysfunction in Major Depressive Disorder: From Receptor and Glial Abnormalities to Circuit Pathology and Mechanism-Based Therapeutic Strategies.","authors":"Xingyu Chen, Qing Chen, Yan Long, Shixiong Huang, Chang Li, Dan Zhu, Xinyu Ben","doi":"10.1016/j.brainresbull.2026.112206","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.112206","url":null,"abstract":"<p><p>Major depressive disorder is a heterogeneous psychiatric disorder that cannot be fully explained by classical monoamine-deficiency models. Increasing evidence indicates that glutamatergic dysfunction provides a central framework for linking molecular, glial, synaptic, and circuit-level abnormalities in depression. This narrative review focuses on glutamatergic dysregulation as the organizing mechanism of major depressive disorder. We summarize core abnormalities involving context-dependent N-methyl-D-aspartate receptor dysfunction, impaired α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated synaptic plasticity, altered metabotropic glutamate receptor signaling, and disrupted astrocytic excitatory amino acid transporter 2-mediated glutamate clearance. These changes converge on excitation-inhibition imbalance, leading to unstable cortical-limbic activity and contributing to emotional dysregulation, anhedonia, cognitive impairment, and impaired stress adaptation. We further discuss upstream mechanisms that regulate glutamatergic dysfunction, including brain-derived neurotrophic factor/mammalian target of rapamycin signaling, neuroinflammation, epigenetic regulation, and microbiota-gut-brain axis-related peripheral crosstalk. At the circuit level, we emphasize abnormalities in the prefrontal cortex-amygdala, amygdala-nucleus accumbens, prefrontal cortex-hippocampus, and lateral habenula pathways. We also consider how monoaminergic and opioid systems modulate glutamate-dependent synaptic and reward-circuit plasticity. Finally, we review therapeutic implications, including ketamine and related N-methyl-D-aspartate receptor modulators, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor facilitation, astrocyte-targeted strategies, anti-inflammatory interventions, circuit-based neuromodulation, and biomarker-guided patient stratification. By centering diverse pathological findings around glutamatergic dysfunction, this review provides a focused mechanistic framework for understanding major depressive disorder and developing precision, mechanism-based treatments.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"112206"},"PeriodicalIF":4.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340919","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":"CD55-targeted modulation of C3-mediated microglia polarization improves perioperative neurocognitive disorders in male mice.","authors":"Qingyu Tian, Huanhuan Zhang, Xiuning Zhang, Hongjie Huang, Ruoxuan Sun, Shijie Cui, Juan Shao, Li Song, Xiaojuan Qie","doi":"10.1016/j.brainresbull.2026.112183","DOIUrl":"10.1016/j.brainresbull.2026.112183","url":null,"abstract":"<p><strong>Background: </strong>Perioperative neurocognitive disorders (PND) are common postoperative complications driven by neuroinflammation and an imbalance in microglial M1/M2 polarization. Complement component 3 (C3) is elevated in PND, while CD55 inhibits C3 activation. Whether CD55 regulates PND via C3 remains unclear.</p><p><strong>Methods: </strong>A PND mouse model and an lipopolysaccharide (LPS)-induced BV2 model were established. Lentivirus-mediated CD55/C3 overexpression was performed. Cognitive function, neuronal injury, inflammation, microglial polarization, and CD55/C3 expression were assessed using behavioral tests, HE staining, ELISA, immunofluorescence, RT-qPCR, and WB.</p><p><strong>Results: </strong>PND mice exhibited cognitive impairment, hippocampal neuronal damage, elevated levels of pro-inflammatory cytokines and C3, and reduced CD55 expression. Overexpression of CD55 improved cognitive function, alleviated damage and inflammation, and suppressed C3. It also restored the balance of M1/M2 markers in BV2 cells. Overexpression of C3 reversed the protective effects of CD55 both in vitro and in vivo.</p><p><strong>Conclusion: </strong>CD55 alleviates PND by regulating complement C3, which may be related to promoting the polarization of microglia toward the M2 phenotype. We have preliminarily identified a potential regulatory target for PND.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"112183"},"PeriodicalIF":4.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340918","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":"Fetal brain volumes in complete vascular ring: A cross-sectional MRI study","authors":"Jing-Ya Ren,&nbsp;Chang-An Chen,&nbsp;Ming Zhu,&nbsp;Xia Zhang,&nbsp;Yao Li,&nbsp;Su-Zhen Dong","doi":"10.1016/j.brainresbull.2026.112181","DOIUrl":"10.1016/j.brainresbull.2026.112181","url":null,"abstract":"&lt;div&gt;&lt;ul&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;Fetuses with complete vascular rings showed smaller adjusted regional brain volumes.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;Thalamic and lentiform nucleus proportions were smaller relative to intracranial volume.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;No group-by-gestational-age interaction survived correction in the primary models.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;/ul&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The association between complete vascular ring (CVR) and prenatal brain development remains poorly characterized.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;The association between complete vascular ring (CVR) and prenatal brain development remains poorly characterized.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To compare global and regional fetal brain volumes between fetuses with CVR and controls, accounting for gestational age (GA), fetal sex, and estimated fetal weight.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;To compare global and regional fetal brain volumes between fetuses with CVR and controls, accounting for gestational age (GA), fetal sex, and estimated fetal weight.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this retrospective single-center study, 70 prenatally diagnosed CVR fetuses and 200 GA-matched controls with normal brain anatomy (22–37 weeks) underwent 1.5-T fetal MRI. Motion-corrected three-dimensional brain reconstructions were generated by slice-to-volume registration, and 19 regions were automatically segmented using a deep-learning pipeline. Linear regression included continuous GA, group, their interaction, fetal sex, and estimated fetal weight. Regional-to-intracranial volume ratios and sensitivity analyses incorporating maternal body mass index were evaluated. Multiple comparisons were controlled using the Benjamini–Hochberg procedure.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;In this retrospective single-center study, 70 prenatally diagnosed CVR fetuses and 200 GA-matched controls with normal brain anatomy (22–37 weeks) underwent 1.5-T fetal MRI. Motion-corrected three-dimensional brain reconstructions were generated by slice-to-volume registration, and 19 regions were automatically segmented using a deep-learning pipeline. Linear regression included continuous GA, group, their interaction, fetal sex, and estimated fetal weight. Regional-to-intracranial volume ratios and sensitivity analyses incorporating maternal body mass index were evaluated. Multiple comparisons were controlled using the Benjamini–Hochberg procedure.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;At the 28-week reference age, adjusted supratentorial brain, cortical gray matter, white matter, thalamic, lentiform nucleus, brainstem, and lateral ventricular volumes were smaller in the CVR group (all false-discovery-rate-adjusted P &lt; 0.05). Intracranial volume did not differ significantly. Thalamic, lentiform nucleus, brainstem, and lateral ventricular proportions were also smaller. No group-by-GA interaction survived correction in the primary model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;At the 28-week reference age, adjusted supratentorial brain","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"246 ","pages":"Article 112181"},"PeriodicalIF":4.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149243078","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":"S-equol mitigates anxiety-like behaviors associated with acute hyperuricemia by restoring neuronal excitability in the medial prefrontal cortex","authors":"Yue-Lian Sun,&nbsp;Xiao-Rui Duan,&nbsp;Yu-Xuan Shi,&nbsp;Wen-Yong You,&nbsp;Zhao Tang,&nbsp;Yong-Jing Gao,&nbsp;Huan-Jun Lu,&nbsp;Xiao-Bo Wu","doi":"10.1016/j.brainresbull.2026.112192","DOIUrl":"10.1016/j.brainresbull.2026.112192","url":null,"abstract":"<div><div>Hyperuricemia (HUA) is a prevalent metabolic disorder closely linked to neuropsychiatric symptoms, including emotional disturbances. However, the neural mechanisms underlying this association remain largely unexplored. We established a mouse model of acute HUA by administering potassium oxonate (PO) and hypoxanthine (HX) intraperitoneally to investigate its effects on emotional behaviors and neural activity in the medial prefrontal cortex (mPFC). The HUA mice exhibited typical hyperuricemia and renal morphological abnormalities, along with increased anxiety-like behaviors, but showed no alterations in mechanical/thermal pain sensitivity or depressive-like behaviors. Immunofluorescence c-Fos mapping revealed extensive activation in emotion-related brain regions, such as the mPFC, paraventricular thalamus (PVT), anterior insular cortex (aIC), lateral hypothalamus (LH), and basolateral amygdala (BLA). Whole-cell patch-clamp recordings demonstrated that HUA was associated with reduced intrinsic excitability of mPFC layer V/VI pyramidal neurons, indicated by a lower firing rate, higher rheobase, and decreased membrane input resistance. Additionally, it was associated with alterations in the excitatory/inhibitory (E/I) synaptic balance, including changes the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). Notably, the reduction in mPFC neuronal excitability was comparable between sexes, although female HUA mice displayed less pronounced synaptic alterations in response to HUA. S-equol, a selective estrogen receptor beta ligand, ameliorated anxiety-like behaviors associated with HUA. Electrophysiological analyses revealed that S-equol appeared to restore the intrinsic excitability of mPFC pyramidal neurons in both sexes, although it did not significantly alter E/I synaptic balance. However, its behavioral effects exhibited sex-dependent differences: S-equol significantly ameliorated anxiety-like behaviors in both sexes, with the specific behavioral domains affected varying between males and females. The results suggest that HUA may be linked to anxiety-like behaviors, potentially involving reduced excitability of mPFC pyramidal neurons. Furthermore, S-equol may exert anxiolytic effects in association with restored neuronal excitability, independently of detectable changes in E/I synaptic balance. Together, this study offers new insights into the neurobiological mechanisms underlying HUA-related emotional disorders and identifies sex-specific potential therapeutic targets.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"246 ","pages":"Article 112192"},"PeriodicalIF":4.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262840","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":"Mobile EEG reveals age-dependent cognitive-motor interference with increasing motor task complexity- A cross-sectional study","authors":"Bettina Wollesen,&nbsp;Leoni Winter,&nbsp;Klaus Gramann,&nbsp;Janna Protzak","doi":"10.1016/j.brainresbull.2026.112173","DOIUrl":"10.1016/j.brainresbull.2026.112173","url":null,"abstract":"<div><div>This study examined age-related differences in behavior and brain dynamics underlying cognitive–motor interference (CMI) during motor dual-tasks (DT) with increasing motor task complexity. Behavioral performance and electrocortical activity were assessed in 19 younger adults (11 males, 8 females; 25.5 ± 2.3 years) and 11 older adults (6 males, 5 females; 72.6 ± 4.6 years) using mobile electroencephalography (EEG). Participants performed an oddball choice-reaction task under three conditions: sitting, standing, and treadmill walking. Event-related potential (ERPs; P1, N1, P3) amplitudes and latencies, response times, postural sway, and gait parameters were recorded to evaluate CMI. Data were analyzed using repeated-measures ANOVAs with within-subject factors of motor condition and stimulus type and age group as a between-subject factor. Older adults exhibited reduced step length compared to younger adults, but no DT-related changes in gait or postural sway were observed. Response times were generally slower in older adults and increased from sitting to standing and walking whereas younger adults showed slowing only from sitting to standing. Early sensory ERP components (P1, N1) demonstrated increased amplitudes with higher motor demands. The P3 component was reduced in amplitude in both groups during walking, with delayed latencies in older adults. For both groups, P3 latencies were associated with prolonged response times. Our findings suggest that this slowing during walking reflects altered cognitive resource allocation, characterized by delayed central information processing and enhanced early visual processing, rather than impaired peripheral motor coordination.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"246 ","pages":"Article 112173"},"PeriodicalIF":4.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227369","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":"Sex-specific classification models for cognitive function in cerebral small vessel disease based on MRE and machine learning","authors":"Xiu Chen,&nbsp;Yingjie Kang,&nbsp;Mei Yang,&nbsp;Xuying Zhu,&nbsp;Jiejing Zhang,&nbsp;Yanwen Huang,&nbsp;Jie Yuan,&nbsp;Wenli Tan","doi":"10.1016/j.brainresbull.2026.112189","DOIUrl":"10.1016/j.brainresbull.2026.112189","url":null,"abstract":"<div><h3>Background</h3><div>Early identification of cognitive impairment is crucial for preventing dementia progression. Magnetic resonance elastography (MRE), combined with traditional imaging markers, provides a novel dimension for cognitive assessment in cerebral small vessel disease (CSVD).</div></div><div><h3>Objective</h3><div>To develop machine learning-based classification models for cognitive function in CSVD patients by integrating MRE brain mechanical parameters, white matter hyperintensity burden, and clinical indicators, and to analyze sex differences in model performance.</div></div><div><h3>Methods</h3><div>100 CSVD subjects underwent MRI scanning including FLAIR for white matter hyperintensities, T1WI for hippocampal atrophy assessment, and MRE for measuring brain mechanical properties across 12 regions. Data were split 8:2 (train:test, stratified); within the training set only, candidate features were ranked by Spearman correlation with MoCA score and a final 13-feature subset was selected by Recursive Feature Elimination (RFE). Subjects were stratified by sex (all-sex: n = 100; male: n = 42; female: n = 58), and 10 machine learning models were compared for each group using 5-fold cross-validation (cvAUC), with SHAP analysis used to interpret feature importance.</div></div><div><h3>Results</h3><div>A 13-feature subset was identified, predominantly MRE stiffness parameters. Naive Bayes performed best in the overall cohort (cvAUC=0.704, 95% CI 0.652–0.756), Extra Trees in males (cvAUC=0.828, 95% CI 0.635–1.000), and XGBoost in females (cvAUC=0.617, 95% CI 0.370–0.863). The female subgroup's confidence interval spanned chance-level discrimination. Using the same feature set, classification accuracy was numerically higher in males than in females. SHAP analysis showed atrophy and white matter hyperintensity burden markers dominated in males, whereas right angular gyrus stiffness and other MRE parameters dominated in the overall cohort and in females.</div></div><div><h3>Conclusion</h3><div>Using an identical feature set and modeling pipeline, machine learning models integrating MRE showed markedly different performance between sexes, indicating that a single sex-agnostic model does not generalize equally to men and women. This performance gap, together with divergent SHAP patterns, underscores the need for sex-stratified modeling in MRE-based cognitive screening for CSVD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"246 ","pages":"Article 112189"},"PeriodicalIF":4.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149294866","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":"Epipharyngeal sensory stimulation is associated with changes in brainstem-cortical functional connectivity and circulating proteomic profiles","authors":"Hideki Sakatani,&nbsp;Ryo Ueda,&nbsp;Khin Khin Tha,&nbsp;Kaoru Murakami,&nbsp;Maho Kitagawa,&nbsp;Shimpei Kubota,&nbsp;Masamitsu Kono,&nbsp;Masaaki Murakami,&nbsp;Muneki Hotomi","doi":"10.1016/j.brainresbull.2026.112185","DOIUrl":"10.1016/j.brainresbull.2026.112185","url":null,"abstract":"<div><div>Neurostimulation has emerged as a potential approach for modulating autonomic and neuroimmune function. Because epipharyngeal mucosa receives sensory innervation from cranial afferents, mechanical stimulation of this region may engage neural pathways. Epipharyngeal abrasive therapy (EAT) involves mechanical and chemical stimulation of the epipharyngeal mucosa and is used clinically for chronic epipharyngitis; however, its central and systemic effects remain poorly understood. This study aimed to investigate whether epipharyngeal stimulation using EAT is associated with changes in brainstem functional connectivity and circulating proteomic profiles in healthy adults. Participants underwent five EAT sessions at 7-day intervals (Protocol A), with restingstate functional MRI performed before, immediately after, and four weeks after the first session. A subset also underwent a control protocol without EAT (Protocol B). Wholebrainstem seed-to-voxel functional connectivity was analyzed. Paired plasma samples collected before and after the first EAT session were analyzed using the SomaScan 11 K assay. Longitudinal analysis identified altered connectivity between the brainstem and subcallosal/medial frontal region, primarily immediately after EAT. A controlled withinsubject analysis identified an EAT-specific increase in connectivity between the brainstem and right temporal pole, extending into the inferior temporal gyrus. Proteomic analysis identified 13 proteins meeting exploratory screening criteria and significant pathway-level enrichment involving RNA metabolism, translation, and extracellular matrix organization. Mechanical and chemical stimulation of the epipharynx was associated with changes in brainstem-cortical functional connectivity and circulating proteomic signatures. These findings suggest that sensory stimulation of the epipharynx may engage cranial sensory afferent–brainstem pathways and contribute to coordinated central neural and peripheral molecular responses.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"246 ","pages":"Article 112185"},"PeriodicalIF":4.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262813","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":"NF-κB as a context-dependent inflammatory regulator of glial programs in epilepsy","authors":"Jing Meng,&nbsp;Wen Luo,&nbsp;Chenyu He,&nbsp;Haohan Luo,&nbsp;Yuxuan He,&nbsp;Chunyan Chen,&nbsp;Nana Zhang,&nbsp;Mingxing Yu,&nbsp;Liang Yu","doi":"10.1016/j.brainresbull.2026.112188","DOIUrl":"10.1016/j.brainresbull.2026.112188","url":null,"abstract":"<div><div>Neuroinflammation is increasingly recognized as an important contributor to epileptogenesis and seizure recurrence, with microglia and astrocytes serving as major regulators of the inflammatory microenvironment. Among the pathways implicated in glia-mediated inflammation, nuclear factor kappa B (NF-κB) occupies a central position by integrating danger signals, metabolic stress, and activity-dependent inputs into inflammatory transcriptional responses. However, current evidence indicates that NF-κB should not be viewed as a uniformly pro-inflammatory pathway or as a single therapeutic switch. Rather, its effects vary according to cell type, upstream signaling context, activation dynamics, and disease stage. In this review, we synthesize evidence on NF-κB-associated signaling in epilepsy across damage-sensing, amplification, metabolic stress, purinergic, and ncRNA-associated modules. We distinguish relatively well-supported pro-inflammatory and neurotoxic inflammatory outputs from more provisional interpretations regarding repair-compatible glial responses. We also evaluate therapeutic strategies that directly or indirectly target NF-κB-related signaling and discuss the limitations of inferring causal NF-κB involvement from multi-target compounds or downstream inflammatory markers. Collectively, this review presents NF-κB as a context-dependent regulator of glia-associated inflammatory outputs in epilepsy and proposes module-specific modulation as a working framework for organizing current evidence and guiding future experimental validation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"246 ","pages":"Article 112188"},"PeriodicalIF":4.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149318209","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}