Brain Sciences最新文献

{"title":"MPTP-Induced D1R-Dependent Dysregulation of Ventral Hippocampal Newborn Cell Pools and Associated Alterations in the Hypothalamic-Pituitary-Adrenal Axis.","authors":"Tingting Di, Kai Zhang, Qian Ru, Wenxuan Yin, Yilin Jin, Ling Chen, Hualing Li","doi":"10.3390/brainsci16101098","DOIUrl":"https://doi.org/10.3390/brainsci16101098","url":null,"abstract":"<p><p><b>Objective:</b> This study investigated how dopaminergic (DAergic) depletion-induced ventral hippocampal neurogenesis triggers hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. <b>Methods</b>: Three-month-old male C57BL/6 mice were subjected to systemic 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or ventral tegmental area (VTA) injections of 1-methyl-4-phenylpyridinium ion (MPP+). We observed tyrosine hydroxylase (TH)-positive cells in the midbrain VTA and hippocampal DA content. We examined BrdU-positive cells in the ventral hippocampal dentate gyrus (vDG) on day 7 (D7) and day 28 (D28) after the BrdU injection. The expression of GAD67 and c-Fos-positive cells reflected the activation of GABAergic neurons. We assessed HPA-axis activity based on the levels of CORT, ACTH, and <i>CRH</i> mRNA. <b>Results</b>: TH immunoreactivity in VTA DAergic neurons and hippocampal DA were markedly reduced on D7 post-MPTP/MPP+ and recovered on D28. The numbers of BrdU-positive cells on D7 and D28 in the vDG were drastically reduced and were remedied by SKF38393 rather than quinpirole. MPTP significantly elevated levels of CORT, ACTH, and <i>CRH</i> mRNA on D28. A SKF38393 injection in the vDG, an AMPA injection in the amBNST, or a muscimol injection in the PVN effectively reversed HPA-axis hyperactivity. <b>Conclusions</b>: These results indicate that VTA DAergic depletion reduces the number of BrdU-labeled newborn cells within the vDG in a D1R-dependent manner. Given our previous work demonstrating unchanged progenitor cell proliferation but impaired survival of vDG newborn neurons under MPTP insult, we propose that disrupted D1R-dependent maintenance of newborn cell populations impairs vHPC-originated glutamatergic input to the amBNST, with associated alterations in the HPA-axis activity.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262662","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":"Circulating Soluble Urokinase Plasminogen Activator Receptor and C-Reactive Protein Concentrations in Adults with High-Functioning Autism.","authors":"Ayşe Kurtulmuş, Beyzanur Ereğli, Betül Nas Dönmez, Aynur Görmez","doi":"10.3390/brainsci16101100","DOIUrl":"https://doi.org/10.3390/brainsci16101100","url":null,"abstract":"<p><p><b>Background:</b> Immune dysregulation has been implicated in the pathophysiology of autism spectrum disorder (ASD). Soluble urokinase plasminogen activator receptor (suPAR) is a stable biomarker of chronic immune activation that has not previously been investigated in ASD. We compared circulating suPAR and C-reactive protein (CRP) concentrations in adults with high-functioning ASD and healthy controls. <b>Methods:</b> In this cross-sectional case-control study, 38 adults with high-functioning ASD and 37 healthy controls were included. Plasma suPAR and CRP concentrations were measured using enzyme-linked immunosorbent assays. Group differences were examined using hierarchical multiple linear regression analyses adjusting for age, sex, body mass index (BMI), and current smoking status. The Autism Spectrum Quotient (AQ) was administered to all participants, and associations between inflammatory biomarkers and autistic traits were assessed using Spearman's rank correlation analyses. Sensitivity analyses were performed after excluding participants with CRP concentrations > 10 mg/L to minimise the potential influence of acute inflammatory conditions. <b>Results:</b> In unadjusted analyses, CRP concentrations were significantly higher in the ASD group (<i>p</i> = 0.006), whereas suPAR concentrations did not differ (<i>p</i> = 0.163). After adjustment for age, sex, BMI, and smoking status, the association between ASD and CRP was no longer significant (<i>p</i> = 0.181), with BMI emerging as the strongest independent predictor of CRP (<i>p</i> < 0.001). No association was observed between ASD and circulating suPAR concentrations in either unadjusted or adjusted analyses (<i>p</i> = 0.612). CRP, but not suPAR, was positively correlated with AQ total scores (<i>p</i> = 0.026). Sensitivity analyses excluding participants with high CRP concentrations yielded findings consistent with the primary analyses. <b>Conclusions:</b> Adults with high-functioning ASD showed no evidence of elevated circulating suPAR concentrations. The attenuation of CRP group differences after adjustment for BMI and smoking status highlights the importance of accounting for metabolic factors when interpreting peripheral inflammatory biomarkers in ASD. These findings do not support elevated suPAR levels in adults with high-functioning ASD.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262565","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":"D-Dimer as a Novel Factor for Recurrent Chronic Subdural Hematoma: Development and Assessment of a New Predictive Nomogram.","authors":"Jiajun Wei, Zhiyang Li, Wenju Wang, Qiang Cai","doi":"10.3390/brainsci16101099","DOIUrl":"https://doi.org/10.3390/brainsci16101099","url":null,"abstract":"<p><strong>Background: </strong>Chronic subdural hematoma (CSDH) is the most common bleeding disorder in the nervous system and has a high recurrence rate, posing a serious threat to the lives of elderly individuals. Early identification and adjustment of the treatment regimen in the perioperative period is crucial. The aim of this study was to create a perioperative predictive nomogram for the early prediction of recurrent CSDH (R-CSDH).</p><p><strong>Methods: </strong>A predictive model was developed including 632 patients with CSDH hospitalized between 1 January 2021 and 31 December 2025 from Wuhan University People's Hospital. The 206 patients from the First People's Hospital of Xiantao City who were hospitalized between 1 January 2022 and 31 December 2025 formed an external validation cohort. Minimum absolute shrinkage was used to optimize feature selection, and logistic regression analysis was applied to further select features and construct a risk prediction model for recurrent CSDH. The calibration, discrimination, and clinical utility of the predictive models were assessed using calibration plots, the C-index, the area under the curve (AUC), and decision curve analysis. External validation was performed by an external validation cohort.</p><p><strong>Findings: </strong>Age, CT hematoma size, hematoma location, atrophy, density, surgical procedure and D-dimer were the predictors for constructing the predictive nomogram, and the results showed that a logistic regression model based on the above seven factors had good calibration and discriminative ability (C-index: 0.925; 95% confidence interval: 0.893-0.957). The AUC of this predictive model was 0.92487. The calibration curve of the nomogram was close to the ideal diagonal. In addition, the decision curve analysis showed that the net benefit of the model was significantly better. External validation demonstrated the reliability of the predictive nomogram.</p><p><strong>Interpretation: </strong>D-dimer was found to be a novel factor for recurrent chronic subdural hematoma. Our study provides clinicians with an accurate tool for identification and early intervention and therapy to reduce the incidence of R-CSDH.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262627","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":"Rethinking Youth Mental Health: Emerging Risks, Transdiagnostic Dimensions, and New Therapeutic Approaches.","authors":"Ilaria Riboldi, Giuseppe Carrà","doi":"10.3390/brainsci16101096","DOIUrl":"https://doi.org/10.3390/brainsci16101096","url":null,"abstract":"<p><p>Mental disorders among children, adolescents, and young adults represent a major and growing public health concern [...].</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262587","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":"The Iron-Mitochondria-Oligodendrocyte Axis: An Emerging Metabolic Framework for Alzheimer's Disease.","authors":"Xinhao Li, Wanxuan Xiao, Mobai Hu, Li Li, Li Lin","doi":"10.3390/brainsci16101097","DOIUrl":"https://doi.org/10.3390/brainsci16101097","url":null,"abstract":"<p><p>With the accelerating process of global aging, Alzheimer's disease (AD) has become an enormous public health burden worldwide. However, its pathogenesis is still not fully understood beyond the classic amyloid-β (Aβ) and tau hypotheses. This review aims to fill this critical knowledge gap by proposing the \"Iron-Mitochondria-Oligodendrocyte Axis (IMOA)\" as a novel metabolic paradigm for deciphering the complex biological mechanisms underlying AD. Specifically, we explicitly aim to address whether this axis functions as a causal, permissive, or modulatory pathway during the early and progressive stages of the disease. We systematically summarize the reciprocal regulatory interactions within this axis, with a focus on how brain iron dyshomeostasis preferentially impacts mitochondria in oligodendrocytes, which are characterized by high metabolic demand. Notably, the IMOA framework highlights disordered iron metabolism as a potential modulatory factor of neurodegeneration by linking iron imbalance to impaired energy metabolism. Excessive intracellular iron induces mitochondrial dysfunction, insufficient energy supply, and reactive oxygen species (ROS) overproduction, thereby triggering oligodendrocyte ferroptosis and myelin degeneration. These events further aggravate neuronal energy depletion, forming a potentially self-sustaining pathological cascade that may operate synergistically with or upstream of Aβ and tau pathologies. This framework not only bridges the logical disconnect between protein accumulation and neuronal degeneration in the Aβ and tau hypothesis but also provides promising targets for multi-target therapeutic strategies. The IMOA offers valuable insights for improving the temporal and spatial precision of AD diagnosis and intervention. Collectively, targeting the IMOA may represent a transformative strategy for developing precision diagnostics and combination therapies to halt or delay the progression of AD.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262701","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":"Post-Stroke Olfactory Dysfunction: Network Mechanisms, Clinical Consequences, and Rehabilitation.","authors":"Thomas Heinbockel, Gursimran Virdi, Lexington Shannon, Sayan Nandi","doi":"10.3390/brainsci16101092","DOIUrl":"https://doi.org/10.3390/brainsci16101092","url":null,"abstract":"<p><p>Stroke is the second leading cause of death after ischemic heart disease, accounting for 10% of all deaths worldwide. Stroke is also a major cause of long-term neurological disability, yet olfactory dysfunction remains an underrecognized consequence of cerebrovascular injury. Smell is rarely evaluated in stroke patients despite its central role in appetite, hedonia, hazard detection, memory, emotional processing, and quality of life. The olfactory system extends from the olfactory epithelium and olfactory bulb to primary olfactory cortex, limbic regions, orbitofrontal cortex, insula, thalamus, hippocampus, broader fronto-limbic networks and cerebellum. The broad anatomical organization of the olfactory system subjects it to frequent perturbation due to stroke or other lesions. Post-stroke olfactory deficits may result from direct injury to olfactory structures, disruption of higher-order olfactory networks, diaschisis, altered sniffing and sensorimotor control, or secondary degeneration. Clinically, these deficits are manifested as hyposmia, anosmia, impaired odor identification, discrimination and memory, altered odor pleasantness, reduced flavor perception, loss of appetite, or reduced odor-guided behavior. Current evidence indicates that olfactory dysfunction can persist into the chronic phase of stroke, although a single prevalence estimate cannot be established because populations, timing, testing methods, and reporting differ substantially across studies. This narrative review provides an overview of stroke-related olfactory dysfunction, emphasizing olfactory pathway anatomy, lesion-relevant mechanisms, clinical consequences, measurement limitations, rehabilitation approaches, and future research priorities. We argue that post-stroke olfactory dysfunction should be understood as a multidimensional network-based disorder rather than a simple binary loss of smell.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262708","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":"Early Postural EMG Dynamics During Optic Flow: Effects of Time, Velocity, Retinal Location and Laterality.","authors":"Milena Raffi, Aurelio Trofè, Alessandra Laffi, Andrea Meoni, Alessandro Piras","doi":"10.3390/brainsci16101090","DOIUrl":"https://doi.org/10.3390/brainsci16101090","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Optic-flow velocity is known to influence postural sway, whereas corresponding electromyographic (EMG) effects may be difficult to detect when muscle activity is averaged over long stimulation periods. We therefore investigated the early temporal organisation of muscle activity following optic-flow onset and examined whether this response was modulated by stimulus velocity, retinal stimulation location, and laterality. <b>Methods:</b> Surface EMG recordings from the tibialis anterior (TA), soleus (SOL), trapezius descendens (TD), and paraspinal C4 muscles were reanalysed from a previously published dataset of 18 healthy adults exposed to radial optic flow at five velocities and three retinal stimulation configurations. RMS activity was quantified in two consecutive post-stimulus windows, 0-200 ms and 200-400 ms, and analysed using repeated-measures ANCOVA with baseline activity entered as a covariate. <b>Results:</b> All four muscles showed greater activation during the 200-400 ms window than during the 0-200 ms window, indicating a consistent temporal increase in EMG activity shortly after optic-flow onset. Additional effects were muscle-specific. In TA, the temporal increase was greater during large-field than peripheral stimulation. In SOL, temporal modulation varied with velocity and body side. TD showed a significant effect of velocity. C4 activity was greater on the right than on the left side. <b>Conclusions:</b> Early postural muscle activity shows a common temporal increase during the first 400 ms after optic-flow onset, together with significant stimulus modulation and laterality. These findings suggest that time-resolved bilateral EMG can reveal aspects of the early postural response that may be hidden when muscle activity is averaged over longer periods.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262544","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":"Pre-Stroke Disability, Stroke Severity and Systemic Inflammation Outweigh Malignancy as Determinants of 90-Day Outcome After Acute Ischemic Stroke: A Single-Center Retrospective Cohort Study.","authors":"Justyna Zielińska-Turek, Jan Gajewski, Małgorzata Dorobek","doi":"10.3390/brainsci16101095","DOIUrl":"https://doi.org/10.3390/brainsci16101095","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Patients with acute ischemic stroke (AIS) and coexisting malignancy have worse outcomes, but it is unclear how much of this reflects malignancy itself rather than pre-stroke function, stroke severity and systemic inflammation. <b>Methods</b>: We retrospectively studied consecutive adults with MRI-confirmed AIS admitted to a neurology department in Warsaw, Poland (2020-2024): 130 with documented malignancy and 100 without. Because every patient with a pre-stroke modified Rankin Scale (mRS) score above 2 had a poor outcome by definition, the primary analysis was restricted to patients with pre-stroke mRS 0-2 (<i>n</i> = 161; 80 versus 81). Logistic models were adjusted sequentially for age, sex, admission NIHSS, pre-stroke mRS and log-transformed C-reactive protein (CRP). <b>Results</b>: Groups were comparable in age and vascular comorbidities. Good 90-day outcome was less frequent with malignancy (40.0% versus 58.0%; <i>p</i> = 0.028), but the association was no longer significant after adjustment for age, sex and admission NIHSS (odds ratio [OR] 1.55, 95% CI 0.69-3.51) and was null after adding pre-stroke mRS and log-CRP (OR 0.67, 0.25-1.81). Admission NIHSS and log-CRP were the consistent independent predictors. Return to within one mRS point of baseline was achieved by 41.5% versus 59.0% (<i>p</i> = 0.011). Among patients with pre-stroke mRS ≤ 2, intravenous thrombolysis rates were similar (22.5% versus 22.2%) and hemorrhagic transformation did not differ (17.4% versus 18.9%). <b>Conclusions</b>: Malignancy added little prognostic information beyond baseline function, stroke severity and systemic inflammation, although a clinically meaningful residual effect cannot be excluded. Among eligible patients, reperfusion appeared equally safe.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262637","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":"Short- and Long-Term Outcomes After MAIA-Guided Biofeedback Training in 346 Patients with Low Vision: A Retrospective Cohort Study.","authors":"Mariana A M Misawa, Aljeena Rahat Qureshi, Ghaliah Nsour, Tina Felfeli, Jack E Teplitsky, Samuel N Markowitz, Monica Daibert Nido","doi":"10.3390/brainsci16101089","DOIUrl":"https://doi.org/10.3390/brainsci16101089","url":null,"abstract":"<p><strong>Purpose: </strong>To describe short- and long-term visual outcomes after MAIA microperimetry biofeedback training (BT) in a low-vision rehabilitation cohort.</p><p><strong>Methods: </strong>Retrospective study of patients who completed BT between 2017 and 2023 (4.1 ± 0.6 sessions). The MAIA device recorded P1 and P2 parameters, defined as the percentage of fundus-tracked fixation points falling within device-defined circular windows centered on the trained retinal locus (TRL).</p><p><strong>Outcomes: </strong>baseline, short-term follow-up (<6 months), and long-term follow-up (≥6 months): P1, P2, best-corrected distance visual acuity (BCVA), near visual acuity, fixation stability (BCEA), mean retinal sensitivity (dB), and reading speed (wpm) MNRead app.</p><p><strong>Results: </strong>A total of 346 participants were included. Median P1 increased from 21.5% at Session 1 to 32.0% at Session 5, and P2 increased from 66.0% to 81.5%. Distance and near visual acuity improved significantly at short-term follow-up but were not significantly different from baseline in the overall cohort at long-term follow-up. Reading speed, BCEA, and mean retinal sensitivity did not show significant longitudinal changes. In an exploratory secondary analysis excluding eyes with worsening BCVA, distance and near visual acuity remained significantly improved at long-term follow-up.</p><p><strong>Conclusions: </strong>MAIA-guided BT was associated with improved within-training fixation performance and short-term visual acuity in this heterogeneous retrospective cohort. Long-term improvement was not demonstrated in the overall cohort; exploratory analyses suggest that underlying disease progression may influence long-term outcomes. Prospective controlled studies are required to determine durability and efficacy.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262643","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":"Glial Contributions to Pain in Neurodegenerative Disease Models: A Systematic Review of Microglial and Astrocytic Evidence.","authors":"Alfonso Alfaro-Rodríguez, José Luis Cortes-Altamirano, Samuel Reyes-Long, Herlinda Bonilla-Jaime, Francisco Jacob Avila-Camacho, Leonardo Miguel Moreno-Villalba, María Elizabeth Herrera-López, Angelica González-Maciel, Beatríz Pérez-Guille, Rosa Eugenia Soriano-Rosales, David Calderon-Guzman, Hugo Juaréz-Olguín","doi":"10.3390/brainsci16101093","DOIUrl":"https://doi.org/10.3390/brainsci16101093","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Pain is a common and disabling non-motor manifestation of neurodegenerative disorders, but the contribution of glial cells to nociceptive processing remains incompletely understood. This systematic review evaluated evidence from preclinical models of neurodegenerative diseases linking microglial and astrocytic activity to pain. <b>Methods:</b> The protocol was prospectively registered in PROSPERO (CRD420251084310), and reporting followed PRISMA 2020. We conducted the original electronic search in PubMed/MEDLINE; during major revision, we conducted supplementary searches in Scopus and Web of Science Core Collection. Across the three sources, we identified 2248 records. After hierarchical deduplication by DOI, PMID, and normalized title, 1567 unique records were screened. Eligible in vivo studies assessed microglial and/or astrocytic alterations together with pain- or nociception-related outcomes. Risk of bias was independently evaluated by two investigators using the SYRCLE tool, and findings were synthesized qualitatively. <b>Results:</b> Twenty-six studies met the eligibility criteria: sixteen examined multiple sclerosis/experimental autoimmune encephalomyelitis (61.5%), seven Parkinson's disease (26.9%), two Alzheimer's disease-related models (7.7%), and one Huntington's disease model (3.8%); no eligible amyotrophic lateral sclerosis study was identified. Pain-related alterations involved inflammatory, neuroimmune, synaptic, and astrocyte-associated pathways, but the evidence was strongly model-dependent. Findings based on individual studies, including early astrocytic contributions in experimental autoimmune encephalomyelitis and altered inflammatory allodynia in an Alzheimer's disease model, are interpreted as study-specific observations requiring replication. <b>Conclusions:</b> The available evidence supports context-dependent associations between glial responses and nociceptive processing; however, marker specificity, EAE predominance, sex and age imbalance, and incomplete reporting of bias control procedures limit causal and cross-disease generalization.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262585","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}