CNS Neuroscience & Therapeutics最新文献

{"title":"PTP1B Modulates Carotid Plaque Vulnerability in Atherosclerosis Through Rab5-PDGFRβ-Mediated Endocytosis Disruption and Apoptosis","authors":"Xiao Zhang,&nbsp;Ran Xu,&nbsp;Tao Wang,&nbsp;Jiayao Li,&nbsp;Yixin Sun,&nbsp;Shengyan Cui,&nbsp;Zixuan Xing,&nbsp;Xintao Lyu,&nbsp;Ge Yang,&nbsp;Liqun Jiao,&nbsp;Wenjing Li","doi":"10.1111/cns.70071","DOIUrl":"10.1111/cns.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Protein tyrosine phosphatase 1B (PTP1B) is a protein tyrosine phosphatase and modulates platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR) signaling in vascular smooth muscle cells (VSMCs) via endocytosis. However, the related molecular pathways that participated in the interaction of endo-lysosome and the trafficking of PDGFR are largely unknown. This study aims to determine the subcellular regulating mechanism of PTP1B to the endo-lysosome degradation of PDGFR in atherosclerotic carotid plaques, thereby offering a potential therapeutic target for the stabilization of carotid plaques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The immunohistochemical staining technique was employed to assess the expression levels of both PDGFR-β and Caspase 3 in stable and vulnerable carotid plaques. Tunnel staining was utilized to quantify the apoptosis of carotid plaques. Live-cell imaging was employed to observe endocytic motility, while cell apoptosis was evaluated through Propidium Iodide staining. In an in vivo experiment, ApoE^−/− mice were administered a PTP1B inhibitor to investigate the impact of PTP1B on atherosclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The heightened expression of PDGFR-β correlates with apoptosis in patients with vulnerable carotid plaques. At the subcellular level of VSMCs, PDGFR-β plays a pivotal role in sustaining a balanced endocytosis system motility, regulated by the expression of Rab5, a key regulator of endocytic motility. And PTP1B modulates PDGFR-β signaling via Rab5-mediated endocytosis. Additionally, disrupted endocytic motility influences the interplay between endosomes and lysosomes, which is crucial for controlling PDGFR-β trafficking. Elevated PTP1B expression induces cellular apoptosis and impedes migration and proliferation of carotid VSMCs. Ultimately, mice with PTP1B deficiency exhibit a reduction in atherosclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results illustrate that PTP1B induces disruption in endocytosis and apoptosis of VSMCs through the Rab5-PDGFRβ pathway, suggesting a potential association with the heightened vulnerability of carotid plaques.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Transcranial Direct Current Stimulation Targeting Dorsolateral Prefrontal Cortex and Orbitofrontal Cortex on Somatic Symptoms in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Controlled Clinical Trial","authors":"Shuxiang Shi,&nbsp;Haijing Huang,&nbsp;Mengke Zhang,&nbsp;Yiming Chen,&nbsp;Weichieh Yang,&nbsp;Fan Wang,&nbsp;Shuqi Kong,&nbsp;Ni Zhou,&nbsp;Zheyi Wei,&nbsp;Shentse Chen,&nbsp;Dongbin Lyu,&nbsp;Chenglin Wu,&nbsp;Qinte Huang,&nbsp;Qinting Zhang,&nbsp;Wu Hong","doi":"10.1111/cns.70110","DOIUrl":"10.1111/cns.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>There is a lack of research on transcranial direct current stimulation (tDCS) for the treatment of somatic symptoms in major depressive disorder (MDD) and the suitable stimulating brain region. We investigated the efficacy of tDCS targeting the dorsolateral prefrontal cortex (DLPFC) versus orbitofrontal cortex (OFC) on depressive somatic symptoms and somatic anxiety in patients with MDD and aimed to identify the appropriate stimulating brain regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this randomized, double-blind, sham-controlled study, a total of 70 patients diagnosed with MDD were randomly allocated into DLPFC group, OFC group, and Sham group. Subjects participated in 2 weeks of 10 primary interventions and subsequently 2-week maintenance interventions weekly (20 min, 2 mA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The DLPFC group showed a more significant improvement in somatic symptoms compared to the Sham group at week 2. At the maintenance and follow-up stages, the DLPFC group outperformed the Sham and OFC groups, but the difference with the Sham group was not significant. Neither active group demonstrated superiority over the Sham group in improving depression and anxiety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, the tDCS targeting DLPFC may be a potentially effective therapeutic target for alleviating somatic symptoms in patients with MDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin-A Attenuates the Inflammatory Response in Sepsis-Associated Encephalopathy by Modulating Oxidative Stress and Inhibiting the ERK/NF-κB Signaling Pathway in Microglia and Astrocytes","authors":"Jing Guo,&nbsp;Dexun Kong,&nbsp;Junchi Luo,&nbsp;Tao Xiong,&nbsp;Fang Wang,&nbsp;Mei Deng,&nbsp;Zhuo Kong,&nbsp;Sha Yang,&nbsp;Jingjing Da,&nbsp;Chaofei Chen,&nbsp;Jinhai Lan,&nbsp;Liangzhao Chu,&nbsp;Guoqiang Han,&nbsp;Jian Liu,&nbsp;Ying Tan,&nbsp;Jiqin Zhang","doi":"10.1111/cns.70096","DOIUrl":"10.1111/cns.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oxidative stress-induced inflammation is a major pathogenic mechanism in sepsis-associated encephalopathy (SAE). We hypothesized that regulation of reactive oxygen species (ROS) by the neuropeptide orexin-A could prevent SAE-induced oxidative stress and inflammation. Therefore, the aim of this study was to investigate the effects of orexin-A on oxidative stress and inflammation in SAE in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adult male mice were treated with orexin-A (250 μg/kg, intranasal administration) to establish a cecal ligation perforation (CLP) model. We performed behavioral tests, observed neuronal damage in the hippocampal region, measured the levels of ROS, NOX2, and observed the structure of mitochondria by transmission electron microscopy. We then examined the inflammatory factors TNF-α and IL-1β, the activation of microglia and astrocytes, the expression of ERK/NF-κB, C3, and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Orexin-A treatment improved cognitive performance in CLP-induced SAE mice, attenuated neuronal apoptosis in the hippocampal region, ameliorated ROS levels and the extent of mitochondrial damage, and reduced protein expression of NOX2 in hippocampal tissue. In addition, orexin-A treatment significantly reduced microglia and astrocyte activation, inhibited the levels of P-ERK and NF-κB, and reduced the release of IL-1β and TNF-α, which were significantly increased after CLP. Finally, Orexin-A treatment significantly decreased the number of C3/glial fibrillary acidic protein (GFAP)-positive cells and increased the number of S100A10/GFAP-positive cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data suggest that orexin-A reduces ROS expression by inhibiting CLP-induced NOX2 production, thereby attenuating mitochondrial damage and neuronal apoptosis. Its inhibition of microglial and A1-type astrocyte activation and inflammation was associated with the ERK/NF-κB pathway. These suggest that orexin-A may reduce cognitive impairment in SAE by reducing oxidative stress-induced inflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention and Treatment of Alzheimer's Disease Via the Regulation of the Gut Microbiota With Traditional Chinese Medicine","authors":"Jinyao Long,&nbsp;Jiani Zhang,&nbsp;Xin Zeng,&nbsp;Min Wang,&nbsp;Ningqun Wang","doi":"10.1111/cns.70101","DOIUrl":"10.1111/cns.70101","url":null,"abstract":"<p>Alzheimer's disease (AD) is caused by a variety of factors, and one of the most important factors is gut microbiota dysbiosis. An imbalance in the gut mincrobiota have been shown to change the concentrations of lipopolysaccharide and short-chain fatty acids. These microorganisms synthesize substances that can influence the levels of a variety of metabolites and cause multiple diseases through the immune response, fatty acid metabolism, and amino acid metabolism pathways. Furthermore, these metabolic changes promote the formation of β-amyloid plaques and neurofibrillary tangles. Thus, the microbiota–gut–brain axis plays an important role in AD development. In addition to traditional therapeutic drugs such as donepezil and memantine, traditional Chinese medicines (TCMs) have also showed to significantly decrease the severity of AD symptoms and suppress the underlying related mechanisms. We searched for studies on the effects of different herbal monomers, single herbs, and polyherbal formulas on the gut microbiota of AD patients and identified the relevant pathways through which the gut microbiota affected AD. We conclude that improvements in the gut microbiota not only decrease the occurrence of inflammatory reactions but also reduce the deposition of central pathological products. Herbal monomers have a stronger effect on improving of central pathology. Polyherbal formulas have the most extensive effect on the gut microbiota in patients with AD. Among the effects of formulas, the anti-inflammatory effect is the most essential and is also the main concern regarding the use of TCMs in treating AD from the viewpoint of the gut microbiota. We hope that this review will be helpful for providing new ideas for the clinical application of TCMs in the treatment of AD.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local Neuronal Activity and the Hippocampal Functional Network Can Predict the Recovery of Consciousness in Individuals With Acute Disorders of Consciousness Caused by Neurological Injury","authors":"Xi Wang,&nbsp;Xingdong Liu,&nbsp;Lin Zhao,&nbsp;Zhiyan Shen,&nbsp;Kemeng Gao,&nbsp;Yu Wang,&nbsp;Danjing Yu,&nbsp;Lin Yang,&nbsp;Ying Wang,&nbsp;Yongping You,&nbsp;Jing Ji,&nbsp;Jiu Chen,&nbsp;Wei Yan","doi":"10.1111/cns.70108","DOIUrl":"10.1111/cns.70108","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;There is limited research on predicting the recovery of consciousness in patients with acute disorders of consciousness (aDOC). The purpose of this study is to investigate the altered characteristics of the local neuronal activity indicated by the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) of the hippocampus network in patients with aDOC caused by neurological injury and to explore whether these characteristics can predict the recovery of consciousness.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Thirty-seven patients with aDOC were included, all of whom completed resting-state functional magnetic resonance imaging (rsfMRI) scans. The patients were divided into two groups based on prognosis of consciousness recovery, 24 patients were in prolonged disorders of consciousness (pDOC) and 13 in emergence from minimally conscious state (eMCS) at 3 months after neurological injury. Univariable and multivariate logistic regression analyses were used to investigate the clinical indicators affecting patients' recovery of consciousness. The ALFF values and FC of the hippocampal network were compared between patients with pDOC and those with eMCS. Additionally, we employed the support vector machine (SVM) method to construct a predictive model for prognosis of consciousness based on the ALFF and FC values of the aforementioned differential brain regions. The accuracy (ACC), area under the curve (AUC), sensitivity, and specificity were used to evaluate the efficacy of the model.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The FOUR score at onset and the length of mechanical ventilation (MV) were found to be significant influential factors for patients who recovered to eMCS at 3 months after onset. Patients who improved to eMCS showed significantly increased ALFF values in the right calcarine gyrus, left lingual gyrus, right middle temporal gyrus, and right precuneus compared to patients in a state of pDOC. Furthermore, significant increases in FC values of the hippocampal network were observed in the eMCS group, primarily involving the right lingual gyrus and bilateral precuneus, compared to the pDOC group. The predictive model constructed using ALFF alone or ALFF combined with FC values from the aforementioned brain regions demonstrated high accuracies of 83.78% and 81.08%, respectively, with AUCs of 95% and 94%, sensitivities of 0.92 for both models, and specificities of 0.92 for both models in predicting the recovery of consciousness in patients with aDOC.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysine Acetyltransferase TIP60 Restricts Nerve Injury by Activating IKKβ/SNAP23 Axis-Mediated Autophagosome-Lysosome Fusion in Alzheimer's Disease","authors":"Wei Wang,&nbsp;Jun Min,&nbsp;Qinghua Luo,&nbsp;Xunhu Gu,&nbsp;Min Li,&nbsp;Xu Liu","doi":"10.1111/cns.70095","DOIUrl":"10.1111/cns.70095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The hyperphosphorylation of Tau protein is considered an important cause of neuronal degeneration in Alzheimer's disease (AD). The disruption of neuronal histone acetylation homeostasis mediated by Tip60 HAT is a common early event in neurodegenerative diseases, but the deeper regulatory mechanism on β-amyloid peptide (Aβ)-induced neurotoxicity and autophagic function in AD is still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>AD models were established both in APP/PS1 mice and Aβ_1–42-treated SH-SY5Y cells. The Morris water maze test (MWM) was performed to examine mouse cognitive function. Neurological damage in the hippocampus was observed by hematoxylin–eosin (H&amp;E), Nissl's, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and NeuN staining. Autophagosome-lysosome fusion was detected by immunohistochemistry, immunofluorescence, and Lyso-Tracker Red staining. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometry. The molecular interactions were verified by co-immunoprecipitation (Co-IP), dual luciferase assays, and ChIP detections. The RNA and autophagy-lysosome-related proteins were assessed by Western blot and RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TIP60 overexpression improved cognitive deficits and neurological damage and restored the impairment of autophagy-lysosomes fusion in vivo. Similarly, the upregulation of TIP60 in Aβ_1–42-treated SH-SY5Y cells suppressed neuronal apoptosis and tau phosphorylation through the activating autophagy-lysosome pathway. Mechanistically, TIP60 activated IKKβ transcription by promoting SOX4 acetylation, thus leading to the translocation of SNAP23 to STX17-contained autophagosomes. Moreover, the protective roles of TIP60 in neuron damage were abolished by the inhibition of SOX4/IKKβ signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, our results highlighted the potential of the TIP60 target for AD and provided new insights into the mechanisms underlying neuroprotection in this disorder.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Optimal Radiotherapy Strategy for Patients With Small Cell Lung Cancer and Brain Metastasis: A Retrospective Analysis","authors":"Qian Zeng,&nbsp;Xianjing Chu,&nbsp;Gang Xiao,&nbsp;Jing Zhang,&nbsp;Yingying Zhang,&nbsp;Bin Long,&nbsp;Lei Yang,&nbsp;Zhaohua Tan,&nbsp;Rongrong Zhou","doi":"10.1111/cns.70102","DOIUrl":"10.1111/cns.70102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extensive-stage small cell lung cancer (ES-SCLC) is a notoriously aggressive malignancy frequently associated with brain metastases (BMs), presenting substantial therapeutic challenges. This study delves into the effectiveness of immunotherapy combined with diverse radiotherapy, especially the influence of brain radiotherapy (BRT) on survival outcomes in the immunotherapy era.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ES-SCLC patients treated at Xiangya Hospital and Xiangya Boai Hospital from February 2020 to June 2024 were retrospectively included. The study focused on patients receiving immune checkpoint inhibitors (ICIs). Metrics included overall survival (OS) and progression-free survival (PFS), employing univariate and multivariate Cox regression models for statistical analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 393 patients with ES-SCLC who received ICIs were included in the study. Within the entire cohort, the presence of baseline BMs did not statistically affect OS or PFS. However, thoracic radiotherapy (TRT) was identified as a favorable prognostic factor for both OS and PFS. BRT demonstrated a beneficial effect on OS across both the general cohort and the baseline_BMs subgroup. In patients from the baseline_BMs subgroup who had previously undergone TRT, ICIs plus BRT did not significantly improve OS compared to ICIs alone. Conversely, for patients who had not received prior TRT, adding BRT to ICIs significantly enhanced OS. Among the patients who underwent BRT, 71 received whole brain radiotherapy (WBRT) while 19 opted for stereotactic radiosurgery (SRS). No significant differences in OS and PFS were observed between the SRS and WBRT modalities. The sequence of ICIs relative to BRT was found to influence PFS adversely. Administering BRT before ICIs (RT-ICI) was associated with worse PFS compared to administering ICIs followed by BRT (ICI-RT). Additionally, no significant differences in OS and PFS were noted among the three subgroups defined by varying intervals between ICIs and BRT. For patients without baseline BMs, TRT and prophylactic cranial irradiation were associated with delayed onset of brain metastases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study underscores the importance of optimizing treatment strategies and considering the timing and integration of radiotherapy and immunotherapy to improve outcomes for patients with ES-SCLC, particularly those at risk of or presenting with BMs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Myeloperoxidase to Reduce Neuroinflammation in X-Linked Dystonia Parkinsonism","authors":"Tiziana Petrozziello,&nbsp;Negin Jalali Motlagh,&nbsp;Ranee Zara B. Monsanto,&nbsp;Dan Lei,&nbsp;Micaela G. Murcar,&nbsp;Ellen B. Penney,&nbsp;D. Cristopher Bragg,&nbsp;Cara Fernandez-Cerado,&nbsp;G. Paul Legarda,&nbsp;Michelle Sy,&nbsp;Edwin Muñoz,&nbsp;Mark C. Ang,&nbsp;Cid Czarina E. Diesta,&nbsp;Can Zhang,&nbsp;Rudolph E. Tanzi,&nbsp;Irfan A. Qureshi,&nbsp;John W. Chen,&nbsp;Ghazaleh Sadri-Vakili","doi":"10.1111/cns.70109","DOIUrl":"10.1111/cns.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Although the genetic locus of X-linked dystonia parkinsonism (XDP), a neurodegenerative disease endemic in the Philippines, is well-characterized, the exact mechanisms leading to neuronal loss are not yet fully understood. Recently, we demonstrated an increase in myeloperoxidase (MPO) levels in XDP postmortem prefrontal cortex (PFC), suggesting a role for inflammation in XDP pathogenesis. Therefore, we hypothesized that inhibiting MPO could provide a therapeutic strategy for XDP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MPO activity was measured by using an MPO-activatable fluorescent agent (MAFA) in human postmortem PFC. Reactive oxygen species (ROS) and MPO activity were measured in XDP-derived fibroblasts and SH-SY5Y cells following MPO inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MPO activity was significantly increased in XDP PFC. Additionally, treatment of cell lines with postmortem XDP PFC resulted in a significant increase in ROS levels. To determine whether increases in MPO activity caused increases in ROS, MPO content was immunodepleted from XDP PFC, which resulted in a significant decrease in ROS in SH-SY5Y cells. Consistently, the treatment with verdiperstat, a potent and selective MPO inhibitor, significantly decreased ROS in both XDP-derived fibroblasts and XDP PFC-treated SH-SY5Y cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, our results suggest that MPO inhibition mitigates oxidative stress and may provide a novel therapeutic strategy for XDP treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neuroprotection of 1,2,4-Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke","authors":"Xuan Liu,&nbsp;Jingning Luo,&nbsp;Jianwen Chen,&nbsp;Ping Huang,&nbsp;Gongyun He,&nbsp;Xueshi Ye,&nbsp;Ruiqi Su,&nbsp;Yaoqiang Lao,&nbsp;Yang Wang,&nbsp;Xiangjun He,&nbsp;Jingxia Zhang","doi":"10.1111/cns.70113","DOIUrl":"10.1111/cns.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). Our former study showed the 1,2,4- triazole derivative (SYS18) had obviously neuroprotection by anti- oxidative stress on rat middle cerebral artery occlusion (MCAO) model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In this study, we continue to investigate its neuroprotection by anti-inflammatory effects and protecting BBB integrity in AIS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>First, its effect on acute inflammation was evaluated by the mice model of increased peritoneal capillary permeability. Then, the MCAO cerebral edema models were built to evaluate its neuroprotection by reducing the neurological score, cerebral edema, improving the biochemical indicators, and pathological damage of brain tissue. At the same time, its protection on blood–brain barrier (BBB) integrity was proved by decreasing the BBB permeability and inhibiting glycocalyx degradation and regulating the BBB tight junction proteins expression of matrix metalloproteinase- 9 (MMP- 9) and claudin- 5 in brain tissue. Meanwhile, pharmacokinetic experiments showed that the compound had good BBB penetration. It has some advantages in the intensity of efficacy compared with the marketed drug edaravone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Based on these findings, SYS18 has a strong potential to become a neuroprotectant in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Border-Associated Macrophages: From Embryogenesis to Immune Regulation","authors":"Tiantong Zhan,&nbsp;Sixuan Tian,&nbsp;Sheng Chen","doi":"10.1111/cns.70105","DOIUrl":"10.1111/cns.70105","url":null,"abstract":"<p>Border-associated macrophages (BAMs) play a pivotal role in maintaining brain homeostasis and responding to pathological conditions. Understanding their origins, characteristics, and roles in both healthy and diseased brains is crucial for advancing our knowledge of neuroinflammatory and neurodegenerative diseases. This review addresses the ontogeny, replenishment, microenvironmental regulation, and transcriptomic heterogeneity of BAMs, highlighting recent advancements in lineage tracing and fate-mapping studies. Furthermore, we examine the roles of BAMs in maintaining brain homeostasis, immune surveillance, and responses to injury and neurodegenerative diseases. Further research is crucial to clarify the dynamic interplay between BAMs and the brain's microenvironment in health and disease. This effort will not only resolve existing controversies but also reveal new therapeutic targets for neuroinflammatory and neurodegenerative disorders, pushing the boundaries of neuroscience.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}