Brain Research最新文献

{"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":"2025-12-19","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":"Chronic dynamic behavioral changes and upregulation of glutamatergic signaling proteins following traumatic brain injury in females","authors":"Caiti-Erin Talty ,&nbsp;Susan F. Murphy ,&nbsp;Pamela J. VandeVord","doi":"10.1016/j.brainres.2025.150115","DOIUrl":"10.1016/j.brainres.2025.150115","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a leading cause of disability worldwide, with approximately 50 % of individuals with mild TBI experiencing persistent, debilitating symptoms. Clinical findings have demonstrated that females are more likely than males to develop chronic symptoms and tend to report greater symptom severity. Despite this, the pathophysiological mechanisms underlying these sex-specific chronic outcomes remain poorly understood. Using a clinically-relevant preclinical model of closed-head controlled impact in adult female rats, we examined affective-like behavior alterations up to twelve weeks post-injury. Injured animals exhibited early increases in risk-taking and disinhibition behaviors, followed by decreased social novelty preference and evidence of increased grooming behavior at eight weeks. Glutamatergic protein expression was measured in the frontal cortex and hippocampus at twelve weeks to assess glutamatergic alterations associated with chronic behavioral outcomes. TBI resulted in elevated expression of N-methyl-D-aspartate receptor subunits GluN1, GluN2A, and GluN2B, along with a decreased GluN2A:GluN2B ratio in the frontal cortex. Additionally, glutamate transporters GLT-1 and GLAST were upregulated in the hippocampus and frontal cortex, respectively. Together, these findings demonstrated that females exhibited dynamic behavioral changes accompanied by region-specific upregulation of glutamatergic signaling proteins. Further investigations are warranted to investigate circuit-level glutamatergic dysfunction and its potential role as a mechanistic driver of chronic TBI-related deficits in females.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150115"},"PeriodicalIF":2.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789793","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":"Ezetimibe mitigates microglial activation in Parkinson’s disease via TLR4/JNK pathway inhibition: evidence from network pharmacology and experimental validation","authors":"You-hai Hua ,&nbsp;Xin-yue Huang ,&nbsp;Jing-jing Ma ,&nbsp;Jin Wu ,&nbsp;Zeng-hui Zhou","doi":"10.1016/j.brainres.2025.150116","DOIUrl":"10.1016/j.brainres.2025.150116","url":null,"abstract":"<div><h3>Objective</h3><div>Neuroinflammation driven by microglial hyperactivation plays a critical role in Parkinson’s disease (PD). Ezetimibe, a cholesterol absorption inhibitor widely used for hyperlipidemia, has recently been implicated in neuroprotection. However, its impact on microglial activation in PD remains poorly understood. This study aimed to investigate the therapeutic potential and mechanisms of ezetimibe in modulating microglial activation in PD model.</div></div><div><h3>Methods</h3><div>Network pharmacology was employed to predict ezetimibe targets in PD, followed by validation in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Protein–protein interaction (PPI) analysis and Gene Ontology (GO) enrichment were used to identify relevant pathways. Molecular docking assessed ezetimibe-TLR4 binding. The effects of ezetimibe on pro-inflammatory mediator production, TLR4/JNK signaling, and microglia-induced dopaminergic neurotoxicity were evaluated using western blotting, qPCR, ELISA, and BV2–SH-SY5Y co-culture assays.</div></div><div><h3>Results</h3><div>Network pharmacology identified 53 common targets between ezetimibe and PD, with TLR4, TNF, and IL-1β as hub genes enriched in inflammatory processes. In BV2 cells, ezetimibe markedly reduced LPS-induced expression and secretion of iNOS, COX-2, Nitric oxide (NO), and IL-6 at both protein and transcriptional levels. Molecular docking revealed a strong binding affinity of ezetimibe to TLR4, although ezetimibe did not alter the basal expression of TLR4. Mechanistically, ezetimibe pretreatment suppressed LPS-induced JNK phosphorylation and AP-1 transcriptional activity, key downstream events of TLR4 activation. Consistently, pharmacological inhibition of TLR4 with TLR4-IN-C34 did not produce additional anti-inflammatory effects, confirming that ezetimibe acts through the TLR4 signaling pathway. Moreover, conditioned medium from ezetimibe-pretreated BV2 cells significantly reduced SH-SY5Y neuronal death, as indicated by decreased PI staining, LDH release, CCK8 assay, tyrosine hydroxylase (TH) protein levels and caspase-3 activation.</div></div><div><h3>Conclusion</h3><div>Ezetimibe suppresses microglial activation by targeting the TLR4/JNK pathway, thereby alleviating dopaminergic neuronal death. These findings highlight ezetimibe as a promising candidate for repurposing in PD therapy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150116"},"PeriodicalIF":2.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789795","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":"Efficacy of transcranial direct current stimulation in children and adolescents with autism spectrum disorder: A systematic review and meta-analysis","authors":"Muhammad Maaz Amjad ,&nbsp;Hadiya Javed ,&nbsp;Muhammad Zuhaz Azeem ,&nbsp;Tuyyab Anwer ,&nbsp;Bilal Wazir Khan ,&nbsp;Muhammad Huzaifa Khattak ,&nbsp;Umer Zaryab Khan ,&nbsp;Muhammad Ahmed Zahoor ,&nbsp;Zobia Tabassum ,&nbsp;Muhammad Ehsan ,&nbsp;Hafiza Sidra ,&nbsp;Habeeb Ahmad ,&nbsp;Sarmad Nazir ,&nbsp;Komal Khan","doi":"10.1016/j.brainres.2025.150114","DOIUrl":"10.1016/j.brainres.2025.150114","url":null,"abstract":"<div><h3>Background</h3><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, repetitive behaviors, and loss of interests. Despite the use of conventional treatment such as medication and behavioral therapy, many children and adolescents still experience significant functional impairments. Recent advances in noninvasive brain stimulation have raised the interest of transcranial direct current stimulation (tDCS) in addressing core symptoms of ASD.</div></div><div><h3>Methods</h3><div>A comprehensive literature search of databases PubMed, Cochrane Library, and Google Scholar for relevant studies was conducted until March 28, 2025. A total of 1,443 records were identified. After duplicate removal and application of inclusion and exclusion criteria, 11 studies contributed to the Meta-analyses, while 28 studies were eligible for the systematic review.</div></div><div><h3>Results</h3><div>In addressing clinical outcomes, tDCS yielded significant improvement in social communication, the pooled data from 4 studies showed significant improvement in social communication (SMD =  − 0.66, 95 % CI [−0.94, −0.39] and p &lt; 0.00001), social awareness was also improved with tDCS (SMD = −0.60; 95 % CI [−1.12, −0.07] and p = 0.03) however, language skill showed no significant improvement (SMD = −0.11; 95 % CI [-0.44, 0.21] and p = 0.50). Moreover, tDCS also showed enhancement in restrictive repetitive behaviors (SMD = −0.60, 95 % CI [−0.85, −0.34] and p &lt; 0.00001). In addition, tDCS generated robust improvements in behavioral symptoms and regulations (SMD = −0.65; 95 % CI [−0.98, −0.32] and p &lt; 0.001). Finally, for overall symptom severity reduction in ASD by tDCS, assessed by SRS score, exhibited statistical improvements (SMD = −0.64; 95 % CI [−0.89, −0.39] and p &lt; 0.00001). However, the pooled analysis of 5 studies assessing ATEC score demonstrated no statistically significant difference (SMD = −0.61; 95 % CI [−1.34, 0.11] and p = 0.10) with high heterogeneity (p = 0.0006, I2 = 80 %). To overcome heterogeneity, we performed a sensitivity analysis, which made the result significant (SMD = −0.95; 95 % CI [−1.41, −0.49] and p &lt; 0.0001) with low heterogeneity (p = 0.16, I2 = 42 %).</div></div><div><h3>Conclusion</h3><div>tDCS appears to be a promising noninvasive therapy for improving social and behavioral symptoms of ASD. However, large-scale, multi-center RCTs with standardized protocols and longer follow-up durations are essential to determine optimal stimulation parameters and to identify which patients will benefit the most from it.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1873 ","pages":"Article 150114"},"PeriodicalIF":2.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780217","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":"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":"2025-12-16","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":"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":"2025-12-15","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":"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":"2025-12-13","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":"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":"2025-12-13","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":"Oxidative Stress-Induced mechanisms in neurodegeneration and Eryptosis: Implications for neurological and systemic disorders","authors":"Marijana Markovic Boras ,&nbsp;Vanja Krulj ,&nbsp;Alma Karahmet ,&nbsp;Kanita Omerbasic ,&nbsp;Asma Nawaz ,&nbsp;Doris Pavković ,&nbsp;Emina K. Sher","doi":"10.1016/j.brainres.2025.150111","DOIUrl":"10.1016/j.brainres.2025.150111","url":null,"abstract":"<div><div>The significant association between development of neurological diseases, like Alzheimer’s, Parkinson’s or depression and oxidative stress occurs from disturbance in the balance between oxidative and antioxidative processes due to chronic stress. Unlike previous reviews that focused only on neurological or systemic diseases, this review discusses the mechanisms that connect oxidative stress and neuroinflammation or eryptosis in both neurological, neurodegenerative, and various systemic diseases, clarifying two completely distinct mechanisms of response to oxidative stress that are common to multiple clinical conditions. This review explores the complex involvement of oxidative damage in neurodegeneration and explains its contribution to inflammation, protein aggregation, and disruption of cellular functions. Crucial components in this process are reactive oxygen and reactive nitrogen species, which can be generated both endogenously or exogenously. Primary sources of ROS in cells are NADPH oxidases, mitochondria, xanthine oxidase and growth factor receptors. Elevated ROS levels disrupt cellular homeostasis and cause oxidative damage and inflammatory responses in neurological disorders characterised by the activation of microglia, astrocytes, and infiltrating CD4 + T cells. Similarly, in systemic disease, this disruption happens through eryptosis. In addition, chronic stress damages antioxidant defence, which further worsens pathological processes. A deeper understanding of the underlying mechanisms provides novel insights into therapeutic strategies for reducing the effects of oxidative stress in both neurological and systemic diseases.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150111"},"PeriodicalIF":2.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751741","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":"2025-12-10","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}