Ruijia You, Bin Sun, Jing Luo, Guanhua Hu, Nan Shao, Wenwen Si
{"title":"Muscone Protects Against Ferroptosis-Induced Injury in Models of Acute Ischemic Stroke by Modulating Snap25 Protein.","authors":"Ruijia You, Bin Sun, Jing Luo, Guanhua Hu, Nan Shao, Wenwen Si","doi":"10.31083/JIN39116","DOIUrl":"https://doi.org/10.31083/JIN39116","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke (AIS) is one of the leading critical neurological conditions globally, resulting in significant adult mortality and disability. Previous studies have demonstrated a close relationship between AIS and the ferroptosis signaling pathway. Muscone, the primary active small-molecule component of musk, is a traditional Chinese medicine that exhibits significant pharmacological effects in reducing stroke injury. However, there is still only limited research on whether muscone can modulate ferroptosis-related injury in AIS, and on the underlying regulatory molecular mechanisms.</p><p><strong>Methods: </strong>We utilized a transmission electron microscope and concurrently performed assays for glutathione peroxidase 4 (GPX4) activity, glutathione (GSH), reactive oxygen species (ROS), lipid peroxides, as well as cell viability and live/dead cell staining to investigate alterations in ferroptosis levels. RNA sequencing, bioinformatics analysis, and western blot (WB) assays were employed to evaluate the changes in synaptosome-associated protein 25 kDa (Snap25) expression levels. Furthermore, molecular docking, surface plasmon resonance (SPR) detection, and molecular dynamics (MD) simulation were implemented to examine the binding affinity and interaction between muscone and Snap25.</p><p><strong>Results: </strong>RNA sequencing technology, bioinformatics analysis, and WB assays revealed that Snap25 was specifically downregulated under simulated AIS conditions. Snap25 knockdown and overexpression experiments were also conducted to elucidate the molecular mechanism by which muscone modulates Snap25 expression, thereby mitigating ferroptosis injury in AIS. Additionally, the results of molecular docking, SPR detection, and MD simulations indicate that muscone has multiple binding sites that allow it to bind directly to the Snap25 protein, thereby stabilizing the protein structure.</p><p><strong>Conclusions: </strong>Our findings suggest that muscone produces an anti-AIS effect in the context of AIS injury by increasing Snap25 protein expression, thus reducing ferroptosis. This investigation offers insight into the anti-stroke mechanism of muscone and introduces a promising new treatment option for clinical AIS management.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"39116"},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560372","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":"Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice.","authors":"Chen Chen, Liang Cao, Mengzhou Xue, Ning Zhu","doi":"10.31083/JIN37182","DOIUrl":"https://doi.org/10.31083/JIN37182","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) is a critical form of stroke with limited treatment options, with secondary brain injury significantly affecting patient outcomes. This study investigated the neuroprotective benefits of idebenone (IDE) in ICH.</p><p><strong>Methods: </strong>An ICH model was established in mice and the temporal progression of oxidative stress and neuroinflammation was evaluated. IDE was then administered intraperitoneally for 3 consecutive days to evaluate its therapeutic effects. Tissue histology was examined after staining with hematoxylin-eosin and TdT-mediated dUTP nick end labeling (TUNEL), while oxidative stress was assessed by western blotting and measurement of malondialdehyde (MDA) levels and neuroinflammation was examined using immunostaining, western blotting, and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Oxidative stress and neuroinflammation peaked at 3 days post-ICH, with elevated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and significant microglial activation. IDE-treated mice had reduced hematoma volumes and improved neurological outcomes. IDE administration decreased Kelch-like ECH-associated protein 1 (Keap1) expression while increasing Nrf2 and NAD(P)H quinone oxidoreductase 1 (NQO1) levels, leading to reduced oxidative damage (<i>p</i> < 0.01, <i>p</i> < 0.05, and <i>p</i> < 0.05, respectively). Moreover, IDE attenuated microglial activation and neutrophil recruitment (<i>p</i> < 0.01, <i>p</i> < 0.01), reduced the levels of matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels (<i>p</i> < 0.05, <i>p</i> < 0.05, and <i>p</i> < 0.05, respectively), and increased IL-10 expression (<i>p</i> < 0.01). IDE also preserved the integrity of the blood-brain barrier (BBB) and reduced brain edema.</p><p><strong>Conclusions: </strong>The results demonstrated that IDE exerts neuroprotective effects in ICH through the mitigation of oxidative stress and neuroinflammation during the acute injury phase. IDE may be a viable therapeutic intervention for ICH.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"37182"},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560369","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":"Does Transcranial Direct Current Stimulation Improve Gait Performances in Healthy Older Adults? A Meta-Analysis.","authors":"Beom Jin Choi, Hajun Lee, Nyeonju Kang","doi":"10.31083/JIN36636","DOIUrl":"10.31083/JIN36636","url":null,"abstract":"<p><strong>Background: </strong>Aging can cause degenerative changes in motor and cognition-related brain areas, presumably by interfering with gait performance in healthy aging populations. We aimed to assess the effects of transcranial direct current stimulation (tDCS) on single- and dual-task walking performances in healthy older adults using meta-analytic approaches.</p><p><strong>Methods: </strong>Eleven studies were qualified based on the inclusion criteria: (a) healthy older adults, (b) treatment = tDCS protocols, (c) control = sham stimulation, (d) gait performance outcomes, and (e) randomized controlled trials using parallel or crossover designs. Effect sizes were estimated using standardized mean difference (SMD) to examine gait performances between active tDCS and sham stimulation. A separate random-effect meta-analysis was performed to determine the effects of tDCS protocols on gait performance during single- and dual-task walking tasks.</p><p><strong>Results: </strong>During single-task walking, the random-effects meta-analysis showed improvements in stride time variability (<i>SMD</i> = 0.203; <i>p</i> = 0.005) and functional mobility (<i>SMD</i> = 0.595; <i>p</i> < 0.001). Moreover, single-task walking performances were improved when the tDCS protocols targeted the primary motor cortex (<i>SMD</i> = 0.424; <i>p</i> = 0.005) and used off-line stimulation (<i>SMD</i> = 0.168; <i>p</i> = 0.008). During dual-task walking, tDCS improved gait speed (<i>SMD</i> = 0.177; <i>p</i> = 0.025) and dual-task cost for gait speed (<i>SMD</i> = 0.548; <i>p</i> < 0.001). Dual-task walking performances were advanced when the tDCS protocols targeted the dorsolateral prefrontal cortex (<i>SMD</i> = 0.231; <i>p</i> = 0.029) and multiple areas including prefrontal cortex (<i>SMD</i> = 0.382; <i>p</i> = 0.001), and applied off-line stimulation (<i>SMD</i> = 0.249; <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>These findings indicate that the tDCS protocols may be a promising tool to support mobility and reduce gait-related challenges in the healthy aging population.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"36636"},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560354","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":"Impairment of White Matter Microstructure in Alcohol Use Disorders and Its Association With Symptoms.","authors":"Shuqi He, Qinghui Zhang, Li Wan, Yang Liu","doi":"10.31083/JIN37538","DOIUrl":"https://doi.org/10.31083/JIN37538","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorder (AUD) is a global health concern, with alcohol abuse leading to structural damage to white matter (WM) fiber tracts, which are crucial for cognitive and emotional functions. However, existing studies often lack systematic evaluations of these changes and their clinical correlations.</p><p><strong>Methods: </strong>Using tract-based spatial statistics (TBSS), we analyzed diffusion tensor imaging (DTI) data from 20 AUD patients and 20 healthy controls. Correlations between fractional anisotropy (FA) values and clinical symptoms, including cognitive dysfunction, depression, and impulsivity, were examined.</p><p><strong>Results: </strong>AUD patients presented significantly decreased FA values in the right corpus callosum, right fornix, left inferior fronto-occipital fasciculus, and left cerebral white matter. The FA peak values of the right fornix and the left cerebral white matter were positively and significantly correlated with cognitive function scores in the AUD group after controlling for smoking status, age, and years of education.</p><p><strong>Conclusions: </strong>Alcohol abuse significantly impairs WM integrity, particularly in regions related to cognitive and emotional regulation. These findings provide structural evidence for the neurobiological mechanisms of AUD and suggest that FA may serve as a potential biomarker for assessing brain damage, guiding therapeutic interventions.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"37538"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Motor Imagery Combined With Action Observation on Motor Function in Stroke Patients.","authors":"Aisha Nakintu, Carmelo Mario Vicario, Lijuan Wang, Shuo Luan, Fengxue Qi","doi":"10.31083/JIN26495","DOIUrl":"https://doi.org/10.31083/JIN26495","url":null,"abstract":"<p><p>Stroke symptoms encompass sensory, cognitive, motor, and psychosocial dysfunctions, with motor impairment being the most prevalent. This impairment significantly contributes to functional incapacity and a diminished quality of life. Stroke rehabilitation strategies primarily aim to promote neural reorganization and motor skill recovery. Among these, motor imagery (MI) and action observation (AO) are distinct therapeutic techniques with unique mechanisms of action. This review begins by analyzing the strengths and limitations of each approach individually and argues that integrating MI and AO therapy could offer a more effective rehabilitation strategy. A thorough evaluation of relevant literature is presented, detailing methodologies, key findings, and implications. The objective is to elucidate the potential benefits and underlying mechanisms of combining these two therapies in stroke rehabilitation. In conclusion, the article advocates for the adoption of combined MI and AO therapy in neurorehabilitation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"26495"},"PeriodicalIF":2.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560356","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}
Michael Bobick, Colin Hanna, John Tyler, Patrick Mohr, Huy Lu, Aidan Powell, Kenneth Blum, David Baron, Kai-Uwe Lewandrowski, Igor Elman, Albert Pinhasov, Mark S Gold, Panayotis K Thanos
{"title":"Exercise Leads to Brain Glucose Metabolism Activation, Increased Dopamine D1 Receptor Levels and is Negatively Correlated with Social Behavior.","authors":"Michael Bobick, Colin Hanna, John Tyler, Patrick Mohr, Huy Lu, Aidan Powell, Kenneth Blum, David Baron, Kai-Uwe Lewandrowski, Igor Elman, Albert Pinhasov, Mark S Gold, Panayotis K Thanos","doi":"10.31083/JIN36646","DOIUrl":"https://doi.org/10.31083/JIN36646","url":null,"abstract":"<p><strong>Background: </strong>Exercise enhances overall health, playing an important role in protecting against diseases that impact brain function. Studies show that physical activity influences several key biological processes, including dopamine signaling, brain glucose metabolism (BGluM), and social behavior.</p><p><strong>Methods: </strong>Male sedentary and chronic exercise rats were examined for dopamine signaling and social behavior. Tyrosine hydroxylase (TH) immunohistochemistry (IHC), and D1 and D2 receptor (D1R and D2R) autoradiography was used to assess dopamine signaling; [18F]-Fluorodeoxyglucose positron emission tomography (FDG PET) was used to measure brain functional connectivity; Crawley's three-chamber sociability test was used to measure social behavior; and Pearson correlation was used to analyze correlations between social interaction and TH, D1R, and D2R binding.</p><p><strong>Results: </strong>Exercised rats demonstrated greater D1R binding within several regions of the caudate putamen and nucleus accumbens. PET image analysis showed significantly higher BGluM in the exercised rats compared with the sedentary controls across several brain regions. These regions are associated with enhanced functional connectivity related to movement, olfaction, cardiovascular function, and predator awareness. Exercise had no significant effect on social interaction. Pearson correlation analysis revealed a significant negative relationship between social interaction and D1R binding.</p><p><strong>Conclusions: </strong>Chronic aerobic exercise did not significantly alter social interaction, TH, or D2R binding. D1R binding was enhanced in the exercise group compared with the sedentary group and was negatively correlated with social interaction. We speculate that approach behavior was attenuated by exercise due to social threat stimulation. Functional connectivity imaging data showed significant glucose metabolic activation within the cuneiform nucleus, which has been previously shown to be critical in defensive behavior. This may explain the lack of significant effect of exercise on approach or exploratory behavior. These findings support the potential of exercise in response to social behavior and the possible attenuation of social behavior towards a social threat or socially inappropriate behavior. Exercise can induce metabolic transience that may assist rats in detecting odors from larger predatory animals.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"36646"},"PeriodicalIF":2.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560367","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}
Nikita I Golushko, Anton D Shevlyakov, Daniil D Martynov, Longen Yang, Murilo S de Abreu, Allan V Kalueff
{"title":"The Emerging Role of Filamin A and <i>FLNA</i> Gene in Central Nervous System Functions: Insights into Neurodevelopment and Disease.","authors":"Nikita I Golushko, Anton D Shevlyakov, Daniil D Martynov, Longen Yang, Murilo S de Abreu, Allan V Kalueff","doi":"10.31083/JIN26489","DOIUrl":"https://doi.org/10.31083/JIN26489","url":null,"abstract":"<p><p>Filamin A (FLNA) is a key protein that binds actin filaments to transmembrane integrins and plays an important role in maintaining cell shape and signaling. In the brain, FLNA is emerging as a critical regulator of neurodevelopment, neuronal migration, actin organization, and neuromodulation. Mutations and/or aberrant expression of the <i>FLNA</i> gene are associated with various brain diseases, such as periventricular heterotopia, Ehlers-Danlos syndrome, and other disorders with impaired cognitive function and brain maldevelopment. Here, we discuss the critical role of FLNA in brain function; its interactions with receptors, integrins, and signaling molecules, as well as the implications of its activity for brain health and disease.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 6","pages":"26489"},"PeriodicalIF":2.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560375","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}
Zhuxiao Xie, Lei Liu, Yanjun Guo, Hanqiu Jiang, Lin Li, Zhixin Qiao, Jiawei Wang
{"title":"Exosomal miR-432-5p, miR-4433b-5p, and miR-599: Biomarkers for Monitoring the Severity of Anti-N-methyl-D-aspartate Receptor Encephalitis.","authors":"Zhuxiao Xie, Lei Liu, Yanjun Guo, Hanqiu Jiang, Lin Li, Zhixin Qiao, Jiawei Wang","doi":"10.31083/JIN37513","DOIUrl":"https://doi.org/10.31083/JIN37513","url":null,"abstract":"<p><strong>Background: </strong>Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare disease with a high disability rate, characterized by acute-to-subacute psychiatric and/or neurological symptoms. Continuous intrathecal antibody synthesis does not correlate with the active phase of encephalitis and antibody titers do not directly reflect the severity of the condition. Currently, there is a lack of biomarkers for disease monitoring. This study focuses on finding novel peripheral blood biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis.</p><p><strong>Methods: </strong>Peripheral blood samples were collected from patients with anti-NMDAR encephalitis, including those with acute-phase (autoimmune encephalitis (AE)-a group) and stable-phase (AE-s group) autoimmune encephalitis. Healthy individuals were included as controls (HC group). We isolated exosomal microRNAs (miRNAs) from the samples and screened differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using quantitative real-time qPCR (RT-qPCR). Furthermore, we conducted a correlation analysis between the expression levels of the screened miRNAs and clinical severity. Finally, we performed functional pathway analysis to explore the underlying mechanisms in anti-NMDAR encephalitis.</p><p><strong>Results: </strong>We found that exosomal miR-432-5p, miR-4433b-5p, and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at various phases of the disease. The expression of miR-432-5p and miR-4433b-5p were negatively correlated with clinical severity. We further identified that key pathways including rhythmic processes and glutamatergic signaling play significant roles in the pathogenesis of anti-NMDAR encephalitis.</p><p><strong>Conclusions: </strong>Our research indicated that exosomal miR-432-5p, miR-4433b-5p, and miR-599 were correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. Moreover, the key functional pathways predicted by these miRNAs may play crucial roles in disease progression.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 5","pages":"37513"},"PeriodicalIF":2.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216056","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}
Zhusheng Chen, Tong Cheng, Haorui Yang, Yongtao Gao, Xiaqing Ma
{"title":"A Review of Treatment Modalities for Comorbid Neuropathic Pain and Depression.","authors":"Zhusheng Chen, Tong Cheng, Haorui Yang, Yongtao Gao, Xiaqing Ma","doi":"10.31083/JIN26523","DOIUrl":"https://doi.org/10.31083/JIN26523","url":null,"abstract":"<p><p>Over the past years, a number of clinical and preclinical investigations have been documented, suggesting treatment strategies and pharmaceuticals for neuropathic pain and depressive disorders, potentially beneficial in cases where these conditions are comorbid. This review lists these potential treatment options and discusses the proposed underlying mechanisms of action and their limitations, in terms of both physiotherapy and pharmacotherapy. Physiotherapy includes electroacupuncture and repetitive transcranial magnetic stimulation therapy, both of which affect neuronal function by altering the physiological state of the neurons. Pharmacological treatments include tricyclic antidepressants, gabapentin, ketamine, minocycline, and Chinese medicine, which alter ion channel activity, affect neurotransmitter release, and exert anti-inflammatory effects. As such, this review may help to improve future research endeavors and therapeutic options for this frequently occurring comorbidity.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 5","pages":"26523"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216094","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":"Neuroprotective Effect of PBCA Nanoparticles Delivering pEGFP-BDNF in a Mouse Model of Intracerebral Hemorrhage.","authors":"Xue Lai, Yu Xiong, Xing Guo, Chunbo Chen","doi":"10.31083/JIN26971","DOIUrl":"https://doi.org/10.31083/JIN26971","url":null,"abstract":"<p><strong>Objectives: </strong>Polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were prepared by emulsion polymerization and loaded with an enhanced green fluorescent protein plasmid (pEGFP) encoding human brain-derived neurotrophic factor (BDNF). This study investigated the potential effects of PBCA-pEGFP-BDNF NPs for the treatment of experimental cerebral hemorrhage mouse model animals.</p><p><strong>Methods: </strong>Eight-week-old male mice (30 ± 5 g) were randomly divided into four groups (sham, intracerebral hemorrhage (ICH), ICH+PBCA NPs, and ICH+ PBCA-pEGFP-BDNF NPs; n = 14). An ICH model was constructed by right striatum injection of bacterial collagenase VII. Neurological function was evaluated by modified Garcia score after treatment of ICH mice with PBCA-pEGFP-BDNF NPs. The area of cerebral hematoma was measured and the water content of brain tissues was calculated by the wet/dry ratio method. Finally, immunofluorescence staining was used to detect neuron-specific nuclear protein (NeuN) positive cells around hematomas. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and western blot were used to detect inflammatory BDNF, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and either interleukin-1 beta (IL-1β) mRNA or protein levels.</p><p><strong>Results: </strong>Treatment with PBCA-pEGFP-BDNF NPs significantly improved neurological function and reduced acute brain edema and neuroinflammation in the mouse model of ICH. qPCR, ELISA, and western blot results showed that PBCA-pEGFP-BDNF NPs increased BDNF expression, inhibited NF-κB signaling pathway activity, and decreased the levels of inflammatory factors (IL-6, TNF-α, IL-1β) when compared with the recombinant plasmid pEGFP-BDNF.</p><p><strong>Conclusion: </strong>PBCA-pEGFP-BDNF NPs improves neurological function in experimental ICH mice at least in part related to increased BDNF expression and decreased p65 NF-κB signaling axis activation, suggesting that PBCA NPs might be a suitable pEGFP-BDNF-carrying delivery system for ICH treatment.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 5","pages":"26971"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216079","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}