CNS Neuroscience & Therapeutics最新文献

{"title":"The role of visual rating and automated brain volumetry in early detection and differential diagnosis of Alzheimer's disease","authors":"Yingren Mai,&nbsp;Zhiyu Cao,&nbsp;Lei Zhao,&nbsp;Qun Yu,&nbsp;Jiaxin Xu,&nbsp;Wenyan Liu,&nbsp;Bowen Liu,&nbsp;Jingyi Tang,&nbsp;Yishan Luo,&nbsp;Wang Liao,&nbsp;Wenli Fang,&nbsp;Yuting Ruan,&nbsp;Ming Lei,&nbsp;Vincent C. T. Mok,&nbsp;Lin Shi,&nbsp;Jun Liu,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1111/cns.14492","DOIUrl":"10.1111/cns.14492","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Medial temporal lobe atrophy (MTA) is a diagnostic marker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the accuracy of quantitative MTA (QMTA) in diagnosing early AD is unclear. This study aimed to investigate the accuracy of QMTA and its related components (inferior lateral ventricle [ILV] and hippocampus) with MTA in the early diagnosis of MCI and AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method<b>s</b></h3>\u0000 \u0000 <p>This study included four groups: normal (NC), MCI stable (MCIs), MCI converted to AD (MCIs), and mild AD (M-AD) groups. Magnetic resonance image analysis software was used to quantify the hippocampus, ILV, and QMTA. MTA was rated by two experienced neurologists. Receiver operating characteristic area under the curve (AUC) analysis was performed to compare their capability in differentiating AD from NC and MCI, and optimal thresholds were determined using the Youden index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>QMTA distinguished M-AD from NC and MCI with higher diagnostic accuracy than MTA, hippocampus, and ILV (AUC_NC = 0.976, AUC_MCI = 0.836, AUC_MCIs = 0.894, AUC_MCIc = 0.730). The diagnostic accuracy of QMTA was superior to that of MTA, the hippocampus, and ILV in differentiating MCI from AD. The diagnostic accuracy of QMTA was found to remain the best across age, sex, and pathological subgroups analyzed. The sensitivity (92.45%) and specificity (90.64%) were higher in this study when a cutoff value of 0.635 was chosen for QMTA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>QMTA may be a better choice than the MTA scale or the associated quantitative components alone in identifying AD patients and MCI individuals with higher progression risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49672035","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":"Regulatory mechanism of circular RNAs in neurodegenerative diseases","authors":"Feng Xiao,&nbsp;Zhi He,&nbsp;Siqi Wang,&nbsp;Jiamei Li,&nbsp;Xiaolan Fan,&nbsp;Taiming Yan,&nbsp;Mingyao Yang,&nbsp;Deying Yang","doi":"10.1111/cns.14499","DOIUrl":"10.1111/cns.14499","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurodegenerative disease is a collective term for a category of diseases that are caused by neuronal dysfunction, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Circular RNAs (circRNAs) are a class of non-coding RNAs without the 3′ cap and 5′ poly(A) and are linked by covalent bonds. CircRNAs are highly expressed in brain neurons and can regulate the pathological process of neurodegenerative diseases by affecting the levels of various deposition proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review is aiming to suggest that the majority of circRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically summarized the pathological features of neurodegenerative diseases and the regulatory mechanisms of circRNAs in various types of neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Neurodegenerative disease main features include intercellular ubiquitin–proteasome system abnormalities, changes in cytoskeletal proteins, and the continuous deposition of insoluble protein fragments and inclusion bodies in the cytoplasm or nucleus, resulting in impairment of the normal physiological processes of the neuronal system. CircRNAs have multiple mechanisms, such as acting as microRNA sponges, binding to proteins, and regulating transcription. CircRNAs, which are highly stable molecules, are expected to be potential biomarkers for the pathological detection of neurodegenerative diseases such as AD and PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this review, we describe the regulatory roles and mechanisms of circRNAs in neurodegenerative diseases and aim to employ circRNAs as biomarkers for the diagnosis and treatment of neurodegenerative diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49672034","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":"A TGF-β signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response","authors":"Wei-Wei Duan,&nbsp;Li-Ting Yang,&nbsp;Jian Liu,&nbsp;Zi-Yu Dai,&nbsp;Ze-Yu Wang,&nbsp;Hao Zhang,&nbsp;Xun Zhang,&nbsp;Xi-Song Liang,&nbsp;Peng Luo,&nbsp;Jian Zhang,&nbsp;Zao-Qu Liu,&nbsp;Nan Zhang,&nbsp;Hao-Yang Mo,&nbsp;Chun-Run Qu,&nbsp;Zhi-Wei Xia,&nbsp;Quan Cheng","doi":"10.1111/cns.14489","DOIUrl":"10.1111/cns.14489","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The dysregulation of TGF-β signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-β signaling in glioma is currently unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. “ELMER v.2” was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In glioma, a TGF-β signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-β signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A prognostic lncRNA signature of TGF-β signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230806","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":"Eomesodermin expression in CD4+T-cells associated with disease progression in amyotrophic lateral sclerosis","authors":"Sheng Chen,&nbsp;Xiao Huan,&nbsp;Chun-Zuan Xu,&nbsp;Su-Shan Luo,&nbsp;Chong-Bo Zhao,&nbsp;Hua-Hua Zhong,&nbsp;Xue-Ying Zheng,&nbsp;Kai Qiao,&nbsp;Yi Dong,&nbsp;Ying Wang,&nbsp;Chang-Yun Liu,&nbsp;Hua-Pin Huang,&nbsp;Yan Chen,&nbsp;Zhang-Yu Zou","doi":"10.1111/cns.14503","DOIUrl":"10.1111/cns.14503","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To clarify the role of Eomesodermin (EOMES) to serve as a disease-relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4⁺T subsets in amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T-cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1-year longitudinal follow-ups, the ALSFRS-R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the derivation cohort, the CD4⁺EOMES⁺T-cell subsets were significantly increased (<i>p</i> &lt; 0.001). EOMES⁺ subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4⁺EOMES⁺T-cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (<i>p</i> = .010) and worse prognosis (<i>p</i> = .003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We demonstrated that increased CD4⁺EOMES⁺T-cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230807","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":"Fine-grained features characterize hippocampal and amygdaloid change pattern in Parkinson's disease and discriminate cognitive-deficit subtype","authors":"Lingyu Zhang,&nbsp;Pengfei Zhang,&nbsp;Qunxi Dong,&nbsp;Ziyang Zhao,&nbsp;Weihao Zheng,&nbsp;Jing Zhang,&nbsp;Xiping Hu,&nbsp;Zhijun Yao,&nbsp;Bin Hu","doi":"10.1111/cns.14480","DOIUrl":"10.1111/cns.14480","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To extract vertex-wise features of the hippocampus and amygdala in Parkinson's disease (PD) with mild cognitive impairment (MCI) and normal cognition (NC) and further evaluate their discriminatory efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>High-resolution 3D-T1 data were collected from 68 PD-MCI, 211 PD-NC, and 100 matched healthy controls (HC). Surface geometric features were captured using surface conformal representation, and surfaces were registered to a common template using fluid registration. The statistical tests were performed to detect differences between groups. The disease-discriminatory ability of features was also tested in the ensemble classifiers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The amygdala, not the hippocampus, showed significant overall differences among the groups. Compared with PD-NC, the right amygdala in MCI patients showed expansion (anterior cortical, anterior amygdaloid, and accessory basal areas) and atrophy (basolateral ventromedial area) subregions. There was notable atrophy in the right CA1 and hippocampal subiculum of PD-MCI. The accuracy of classifiers with multivariate morphometry statistics as features exceeded 85%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PD-MCI is associated with multiscale morphological changes in the amygdala, as well as subtle atrophy in the hippocampus. These novel metrics demonstrated the potential to serve as biomarkers for PD-MCI diagnosis. Overall, these findings from this study help understand the role of subcortical structures in the neuropathological mechanisms of PD cognitive impairment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10805398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230808","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":"Oligomer-Aβ42 suppress glioma progression via potentiating phagocytosis of microglia","authors":"Jie Lu,&nbsp;Zhenning Wang,&nbsp;Zhenqiang He,&nbsp;Yang Hu,&nbsp;Hao Duan,&nbsp;Zihao Liu,&nbsp;Depei Li,&nbsp;Sheng Zhong,&nbsp;Jiaoyan Ren,&nbsp;Guojun Zhao,&nbsp;Yonggao Mou,&nbsp;Maojin Yao","doi":"10.1111/cns.14495","DOIUrl":"10.1111/cns.14495","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Glioma is characterized by an immunosuppressed environment and a poor prognosis. The accumulation of Amyloid <i>β</i> (A<i>β</i>) leads to an active environment during the early stages of Alzheimer's disease (AD). A<i>β</i> is also present in glioma tissues; however, the biological and translational implications of A<i>β</i> in glioma are elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunohistochemical (IHC) staining, Kaplan–Meier (KM) survival analysis and Cox regression analysis on a cohort of 79 patients from our institution were performed to investigate the association between A<i>β</i> and the malignancy of glioma. Subsequently, the potential of oligomer-A<i>β</i>42 (OA<i>β</i>42) to inhibit glioma growth was investigated <i>in vivo</i> and <i>in vitro</i>. Immunofluorescence staining and phagocytosis assays were performed to evaluate the activation of microglia. Finally, RNA-seq was utilized to identify the predominant signaling involved in this process and <i>in vitro</i> studies were performed to validate them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A positive correlation between A<i>β</i> and a favorable prognosis was observed in glioma. Furthermore, OA<i>β</i>42 suppressed glioma growth by enhancing the phagocytic activity of microglia. Insulin-like growth factor 1 (IGF-1) secreted by OA<i>β</i>42-activated microglia was essential in the engulfment process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study proved an anti-glioma effect of A<i>β</i>, and microglia could serve as a cellular target for treating glioma with OA<i>β</i>42.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230810","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":"Long-term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity","authors":"Yi-Shu Yin,&nbsp;Yuan-Bing Zhu,&nbsp;Jun-Lian Liu,&nbsp;Quan-Chun Fan,&nbsp;Xiao-Rui Wu,&nbsp;Shuang Zhao,&nbsp;Jia-Ping Wang,&nbsp;Yu Liu,&nbsp;Yong-Zhi Li,&nbsp;Wei-Hong Lu","doi":"10.1111/cns.14438","DOIUrl":"10.1111/cns.14438","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to identify changes in hippocampus synaptic plasticity under LSCS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (<i>p</i> &lt; 0.05; <i>p</i> &lt; 0.05, respectively). Meanwhile, LTP was significantly impaired (<i>p</i> &lt; 0.0001), and currents in the NMDAR channel were also significantly reduced (<i>p</i> &lt; 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230809","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 association between hemoglobin concentration and clinical outcomes after aneurysmal subarachnoid hemorrhage: Insights from the LongTEAM registry","authors":"Fa Lin,&nbsp;Changyu Lu,&nbsp;Runting Li,&nbsp;Yu Chen,&nbsp;Heze Han,&nbsp;Yuanli Zhao,&nbsp;Xiaolin Chen,&nbsp;Jizong Zhao","doi":"10.1111/cns.14506","DOIUrl":"10.1111/cns.14506","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study is to explore whether preoperative hemoglobin levels could serve as a prospective biomarker for early brain injury in patients with aneurysmal subarachnoid hemorrhage (aSAH). This investigation seeks to discern its association with postoperative complications and unfavorable clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive analysis of data derived from the LongTeam registry, including patients with aSAH diagnosed between January 2015 and September 2021. These patients were stratified into three distinct groups based on their hemoglobin levels: anemic, standard, and elevated HGB. We employed logistic models featuring spline transformations to assess the relationship between HGB levels and in-hospital complications. Furthermore, a multivariate Cox proportional hazard model was employed to estimate the impact of elevated hemoglobin levels on the hazard function, which was elucidated through Kaplan–Meier curves.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study comprised a total of 988 patients, among whom 115 (11.6%) presented preoperative anemia, and 63 (6.4%) exhibited elevated preoperative HGB levels. Following adjustments for potential confounding factors, no significant disparity in risk was evident between anemic patients and those with standard HGB levels. However, individuals with elevated HGB levels displayed a heightened incidence and an increased risk of developing deep vein thrombosis (DVT, odds ratio [OR] = 2.39, 95% confidence interval [CI] = 1.16–4.91, <i>p</i> = 0.018; hazard ratio [HR] = 2.05, 95% CI 1.08–3.92, <i>p</i> = 0.015). Aberrant HGB concentrations did not demonstrate an association with other clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings emphasize that abnormal HGB levels show no association with adverse outcomes at the 90 days mark after accounting for clinical confounding factors in patients with aSAH. Simultaneously, the study illuminates the potential of HGB as an early indicator for identifying patients at a heightened risk of developing DVT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230811","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":"Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats","authors":"Xiaohui Chen,&nbsp;Andi Chen,&nbsp;Jianjie Wei,&nbsp;Yongxin Huang,&nbsp;Jianhui Deng,&nbsp;Pinzhong Chen,&nbsp;Yanlin Yan,&nbsp;Mingxue Lin,&nbsp;Lifei Chen,&nbsp;Jiuyun Zhang,&nbsp;Zhibin Huang,&nbsp;Xiaoqian Zeng,&nbsp;Cansheng Gong,&nbsp;Xiaochun Zheng","doi":"10.1111/cns.14486","DOIUrl":"10.1111/cns.14486","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Dexmedetomidine (DEX) has been reported to alleviate hypoxic–ischemic brain damage (HIBD) in neonates. This study aimed to investigate whether DEX improves cognitive impairment by promoting hippocampal neurogenesis via the BDNF/TrkB/CREB signaling pathway in neonatal rats with HIBD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HIBD was induced in postnatal day 7 rats using the Rice-Vannucci method, and DEX (25 μg/kg) was administered intraperitoneally immediately after the HIBD induction. The BDNF/TrkB/CREB pathway was regulated by administering the TrkB receptor antagonist ANA-12 through intraperitoneal injection or by delivering adeno-associated virus (AAV)-shRNA-BDNF via intrahippocampal injection. Western blot was performed to measure the levels of BDNF, TrkB, and CREB. Immunofluorescence staining was utilized to identify the polarization of astrocytes and evaluate the levels of neurogenesis in the dentate gyrus of the hippocampus. Nissl and TTC staining were performed to evaluate the extent of neuronal damage. The MWM test was conducted to evaluate spatial learning and memory ability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The levels of BDNF and neurogenesis exhibited a notable decrease in the hippocampus of neonatal rats after HIBD, as determined by RNA-sequencing technology. Our results demonstrated that treatment with DEX effectively increased the protein expression of BDNF and the phosphorylation of TrkB and CREB, promoting neurogenesis in the dentate gyrus of the hippocampus in neonatal rats with HIBD. Specifically, DEX treatment significantly augmented the expression of BDNF in hippocampal astrocytes, while decreasing the proportion of detrimental A1 astrocytes and increasing the proportion of beneficial A2 astrocytes in neonatal rats with HIBD. Furthermore, inhibiting the BDNF/TrkB/CREB pathway using either ANA-12 or AAV-shRNA-BDNF significantly counteracted the advantageous outcomes of DEX on hippocampal neurogenesis, neuronal survival, and cognitive improvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DEX promoted neurogenesis in the hippocampus by activating the BDNF/TrkB/CREB pathway through the induction of polarization of A1 astrocytes toward A2 astrocytes, subsequently mitigating neuronal damage and cognitive impairment in neonates with HIBD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10805444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41186537","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":"Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non-G-CIMP glioblastomas with unmethylated MGMT promoter: MGMT-dependent roles of GPR81","authors":"Bao-Bao Liang,&nbsp;Yu-Hong Wang,&nbsp;Jing-Jing Huang,&nbsp;Shuai Lin,&nbsp;Guo-Chao Mao,&nbsp;Zhang-Jian Zhou,&nbsp;Wan-Jun Yan,&nbsp;Chang-You Shan,&nbsp;Hui-Zi Wu,&nbsp;Amandine Etcheverry,&nbsp;Ya-Long He,&nbsp;Fang-Fang Liu,&nbsp;Hua-Feng Kang,&nbsp;An-An Yin,&nbsp;Shu-Qun Zhang","doi":"10.1111/cns.14465","DOIUrl":"10.1111/cns.14465","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purposes</h3>\u0000 \u0000 <p>To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (un<i>MGMT</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The discovery-validation approach was planned incorporating a series of G-CIMP−/un<i>MGMT</i> GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP−/un<i>MGMT</i> GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on <i>GPR81</i>, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of <i>MGMT</i> expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP−/un<i>MGMT</i> GBMs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 4","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41186538","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}