CNS Neuroscience & Therapeutics最新文献

{"title":"Olaparib Enhances the Efficacy of Third-Generation Oncolytic Adenoviruses Against Glioblastoma by Modulating DNA Damage Response and p66shc-Induced Apoptosis","authors":"Yida Liu,&nbsp;Sheng Fang,&nbsp;Peiwen Wang,&nbsp;Junwen Zhang,&nbsp;Fusheng Liu","doi":"10.1111/cns.70124","DOIUrl":"10.1111/cns.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Patients with glioblastoma multiforme (GBM) do not benefit from current cancer treatments, and their prognosis is dismal. This study aimed to investigate the potential synergistic effects of TS-2021, a third-generation oncolytic adenovirus, combined with the PARP inhibitor olaparib in GBM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TS-2021’s impact on p66shc-induced apoptosis, DNA damage response, and poly (ADP-ribose) polymerase (PARP) activation was evaluated in GBM cells. The synergistic effect of TS-2021 and olaparib was examined in GBM cell lines and an immunocompetent mouse model of GBM. Mechanistic studies focused on the role of p66shc phosphorylation in the observed effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TS-2021 triggered p66shc-induced apoptosis, DNA damage response, and PARP activation. The combination of TS-2021 and olaparib synergistically increased cell apoptosis and DNA damage and reduced PARP expression compared to monotherapy. Olaparib promoted TS-2021 replication and release in GBM cells. Mechanistically, olaparib combined with TS-2021 upregulated p66shc phosphorylation, enhancing tumor cell apoptosis. In vivo, the combination therapy inhibited tumor growth and prolonged survival, confirming the synergistic effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study is the first to suggest that TS-2021 sensitizes GBM cells with wild-type BRCA1/2 to olaparib. The combination of TS-2021 and olaparib shows a synergistic therapeutic effect against GBM, providing a promising treatment strategy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646234","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":"Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition","authors":"Shuyuan Hu,&nbsp;Yaqin Gu,&nbsp;Limin Hou,&nbsp;Jia Liu,&nbsp;Haiping Zhao,&nbsp;Yumin Luo,&nbsp;Chunxiu Wang,&nbsp;Xunming Ji,&nbsp;Guiyou Liu,&nbsp;Jiangang Duan","doi":"10.1111/cns.70125","DOIUrl":"10.1111/cns.70125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>NLRP3 inflammasome-related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti-inflammatory agents in improving severe CVT prognosis remains controversial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 94 male Sprague–Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In rats, compared with the sham group, NLRP3-related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, <i>p</i> &lt; 0.01; pro-Caspase-1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, <i>p</i> &lt; 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, <i>p</i> &lt; 0.05; pro-IL-1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, <i>p</i> &lt; 0.01), decreased on day 7 in rats (<i>n</i> = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, <i>p</i> &lt; 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, <i>p</i> &lt; 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL-6 levels correlated positively with NIHSS (<i>r</i> = 0.4273, <i>p</i> = 0.0020; <i>r</i> = 0.4938, <i>p</i> = 0.0029) and mRS (<i>r</i> = 0.5349, <i>p</i> = 0.0125; <i>r</i> = 0.6213, <i>p</i> = 0.026), while CSF IL-6 correlated positively with mRS on admission (<i>r</i> = 0.5349, <i>p</i> = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), <i>p</i> &lt; 0.0001) and IL-6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, <i>p</i> &lt; 0.05), accompanying by improvement of neurological deficits and CSF circulation (all <i>p</i> &lt; 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow-up. No significant steroid-related adverse effects were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Short-term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome-related inflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646237","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":"Endothelial Dysfunctions in Blood–Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies","authors":"Qian Yue,&nbsp;Xinyue Leng,&nbsp;Ningqing Xie,&nbsp;Zaijun Zhang,&nbsp;Deguang Yang,&nbsp;Maggie Pui Man Hoi","doi":"10.1111/cns.70079","DOIUrl":"10.1111/cns.70079","url":null,"abstract":"<p>Recent research has shown the presence of blood–brain barrier (BBB) breakdown in Alzheimer's disease (AD). BBB is a dynamic interface consisting of a continuous monolayer of brain endothelial cells (BECs) enveloped by pericytes and astrocytes. The restricted permeability of BBB strictly controls the exchange of substances between blood and brain parenchyma, which is crucial for brain homeostasis by excluding blood-derived detrimental factors and pumping out brain-derived toxic molecules. BBB breakdown in AD is featured as a series of BEC pathologies such as increased paracellular permeability, abnormal levels and functions of transporters, and inflammatory or oxidative profile, which may disturb the substance transportation across BBB, thereafter induce CNS disorders such as hypometabolism, Aβ accumulation, and neuroinflammation, eventually aggravate cognitive decline. Therefore, it seems important to protect BEC properties for BBB maintenance and neuroprotection. In this review, we thoroughly summarized the pathological alterations of BEC properties reported in AD patients and numerous AD models, including paracellular permeability, influx and efflux transporters, and inflammatory and oxidative profiles, and probably associated underlying mechanisms. Then we reviewed current therapeutic agents that are effective in ameliorating a series of BEC pathologies, and ultimately protecting BBB integrity and cognitive functions. Regarding the current drug development for AD proceeds extremely hard, this review aims to discuss the therapeutic potentials of targeting BEC pathologies and BBB maintenance for AD treatment, therefore expecting to shed a light on the future AD drug development by targeting BEC pathologies and BBB protection.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643543","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":"Phospholipase D Family Member 4 Regulates Microglial Phagocytosis and Remyelination via the AKT Pathway in a Cuprizone-Induced Multiple Sclerosis Mouse Model","authors":"Ran Sun,&nbsp;Tengyun Ma,&nbsp;Zheng Zhao,&nbsp;Yan Gao,&nbsp;Juan Feng,&nbsp;Xue Yang","doi":"10.1111/cns.70111","DOIUrl":"10.1111/cns.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Remyelination is an endogenous repair process that is often deficient in multiple sclerosis (MS). Stimulation of remyelination is thought to help limit the progression of MS. This study aimed to investigate the expression pattern and function of a microglial phagocytosis-related gene, phospholipase D family member 4 (PLD4), in a cuprizone (CPZ)-induced MS mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The extent of remyelination was assessed using LFB staining. Myelin phagocytosis assay was used to investigate the effect of Pld4 on microglial phagocytic activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pld4 was upregulated in the corpus callosum during demyelination and remyelination. AAV9-mediated Pld4 deficiency impaired remyelination and reduced the number of Olig2-positive cells. In the corpus callosum of Pld4-deficient mice, the microglial phagocytosis marker MAC2 was reduced, accompanied by inhibition of TrkA/AKT signaling. Similarly, the phagocytosis assay showed that Pld4 knockdown significantly inhibited myelin debris phagocytosis by BV2 cells. The AKT activator SC79 reversed the Pld4 deficiency-induced inhibition of microglial phagocytic activity and rescued the impaired remyelination in Pld4-deficient mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PLD4 is upregulated in CPZ-induced MS and modulates microglial phagocytosis and remyelination via the AKT pathway. Our findings provide experimental evidence for a better understanding of the molecular mechanism of MS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643547","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":"Individualized rTMS Intervention Targeting Sleep Deprivation-Induced Vigilance Decline: Task fMRI-Guided Approach","authors":"Yuanqiang Zhu,&nbsp;Chen Wang,&nbsp;Ziliang Xu,&nbsp;Fan Guo,&nbsp;Yingjuan Chang,&nbsp;Jiali Liu,&nbsp;WenMing Liu,&nbsp;Peng Fang,&nbsp;Minwen Zheng","doi":"10.1111/cns.70087","DOIUrl":"10.1111/cns.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Study Objectives</h3>\u0000 \u0000 <p>Sleep deprivation (SD) is prevalent in our increasingly round-the-clock society. Optimal countermeasures such as ample recovery sleep are often unfeasible, and brief naps, while helpful, do not fully restore cognitive performance following SD. Thus, we propose that targeted interventions, such as repetitive transcranial magnetic stimulation (rTMS), may enhance cognitive performance recovery post-SD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 50 participants for two SD experiments. In the first experiment, participants performed a psychomotor vigilance task (PVT) under three conditions: normal sleep (resting wakefulness), after 24 h of SD, and following a subsequent 30-min nap. We analyzed dynamic changes in PVT outcomes and cerebral responses across conditions to identify the optimal stimulation target. Experiment 2 adopted the same protocol except that, after the nap, 10-Hz, sham-controlled, individualized rTMS was administrated. Then, an analysis of variance was conducted to investigate the ability of stimulation to improve the PVT reaction times.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through task-related functional magnetic resonance imaging, we identified cerebral responses within the right middle frontal gyrus (MFG) as the optimal stimulation target. Subsequent application of individualized 10-Hz rTMS over the right MFG attenuated SD-induced deterioration of vigilance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that combining a brief nap with individualized rTMS can significantly aid the recovery of vigilance following SD. This approach, through modulating neural activity within functional brain networks, is a promising strategy to counteract the cognitive effects of SD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612891","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":"Automated Hematoma Detection and Outcome Prediction in Patients With Traumatic Brain Injury","authors":"Yang Xu,&nbsp;Qiuyu Fu,&nbsp;Mengqi Qu,&nbsp;Junyao Chen,&nbsp;Jianqi Fan,&nbsp;Shike Hou,&nbsp;Lu Lu","doi":"10.1111/cns.70119","DOIUrl":"10.1111/cns.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To develop a tool for automated subtype classification and segmentation of intracranial hemorrhages (ICH) on CT scans of patients with traumatic brain injury (TBI). Furthermore, outcome prediction for patients can effectively facilitate patient management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study presents a cascade framework for two-stage segmentation and multi-label classification. The hematoma region of interest (ROI) is localized, and then the ROI is cropped and resized to the original pixel size before being input into the model again to obtain the segmentation results. In multilabel classification, the mask obtained from automatic segmentation is superimposed onto the corresponding ROI and CT slices, respectively, to constitute the input image. Subsequently, the ROI image is employed as the local network input to obtain local features. Third, the CT image is utilized to construct a feature extraction network to obtain global features. Ultimately, the local and global features are fused dimensions in the pooling layer, and calculated to generate the final retrieval results. For the prediction of 14-day in-hospital mortality, automatically extracted hematoma subtype and volume features were integrated to enhance the widely used CRASH model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proposed segmentation method achieves the best estimates on the Dice similarity coefficient and Jaccard Similarity Index. The proposed multilabel classification method achieved an average accuracy of 95.91%. For mortality prediction, the best model achieved an average area under the receiver operating characteristic curve (AUC) of 0.91 by 5-fold cross-validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed method enhances the precision of hematoma segmentation and subtype classification. In clinical settings, the method can streamline the evaluation of ICH for radiologists, and the automatically extracted features are anticipated to facilitate prognosis assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612886","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":"Postoperative Nodal Efficiency of the Lesional-Hemispheric Hand Motor Area Increasing Potentially Facilitated Motor Recovery for SMA Syndrome","authors":"Shimeng Weng,&nbsp;Zhaoting Meng,&nbsp;Lianwang Li,&nbsp;Jinshi Li,&nbsp;Xing Fan,&nbsp;Zhong Zhang,&nbsp;Yinyan Wang,&nbsp;Tao Jiang,&nbsp;Shengyu Fang","doi":"10.1111/cns.70112","DOIUrl":"10.1111/cns.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Supplementary motor area (SMA) syndrome commonly occurs after glioma resection and requires weeks to months of recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-four glioma patients with SMA syndrome were reviewed and assigned to recovered and non-recovered groups based on whether their motor function recovered on postoperative day 7. To validate the association between variations in nodal properties and recovery time, neuro-navigated repetitive transcranial magnetic stimulation (nrTMS) was applied to stimulate potential nodes. Nine other patients (five nrTMS therapy and four sham-nrTMS treatments) with SMA syndrome with unrecovered motor functions on postoperation day 7 were prospectively enrolled.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The potential nodes of the sensorimotor network related to recovery time were investigated using preoperative and postoperative resting-state functional magnetic resonance imaging, graph theoretical analysis, and dynamic functional connectome analysis. Nodal efficiency of the lesional-hemispheric upper limb region of BA 4 (A4ul_L) increased in the recovered group (preoperative, 0.472 ± 0.027; postoperative, 0.535 ± 0.020; <i>p</i> = 0.0006). The patients in the nrTMS therapy group quickly recovered (12.0 ± 1.6 days) compared to the sham-nrTMS group (29.5 ± 3.8 days, <i>p</i> = 0.0024). Variations in A4ul_L nodal efficiency was negatively correlated with recovery time (<i>r</i> = −0.841; <i>p</i> = 0.0046).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A4ul_L demonstrates enhanced postoperative nodal efficiency and shows therapeutic potential in SMA syndrome recovery, suggesting its viability as a therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612914","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":"Stroke-Induced Renal Dysfunction: Underlying Mechanisms and Challenges of the Brain–Kidney Axis","authors":"Xi Chen,&nbsp;Dong-Xiao Yang,&nbsp;Heng Zhao,&nbsp;Hong-Fei Zhang,&nbsp;Pu Hong","doi":"10.1111/cns.70114","DOIUrl":"10.1111/cns.70114","url":null,"abstract":"<p>Stroke, a major neurological disorder and a leading cause of disability and death, often inflicts damage upon other organs, particularly the kidneys. While chronic kidney disease (CKD) has long been established as a significant risk factor for cerebrovascular disease, stroke can induce renal dysfunction, manifesting as acute kidney injury (AKI) or CKD. Mounting clinical and basic research evidence supports the existence of a bidirectional brain-kidney crosstalk following stroke, implicating specific mechanisms and pathways in stroke-related renal dysfunction. This review analyzes pertinent experimental studies, elucidating the underlying mechanisms of this cerebro-renal interaction following stroke. Additionally, we summarize the current landscape of clinical research investigating brain-kidney interplay and discuss potential challenges in the future. By enhancing our understanding of the scientific underpinnings of brain-kidney crosstalk, this review paves the way for improved treatment strategies and outcomes for stroke patients. Recognizing the intricate interplay between the brain and kidneys after stroke holds profound clinical implications.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612903","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":"Antisense oligonucleotides as a precision therapy for developmental and epileptic encephalopathies","authors":"Paloma García Quilón,&nbsp;Greta Volpedo,&nbsp;Serena Cappato,&nbsp;Loretta Ferrera,&nbsp;Federico Zara,&nbsp;Renata Bocciardi,&nbsp;Antonella Riva,&nbsp;Pasquale Striano","doi":"10.1111/cns.70050","DOIUrl":"10.1111/cns.70050","url":null,"abstract":"<p>Developmental and epileptic encephalopathies (DEEs) comprise a complex spectrum of neurological disorders characterized by neurodevelopmental delay and early-onset seizures primarily caused by diverse genetic mutations. Traditional treatments have largely been symptomatic, focusing on seizure control without addressing the underlying genetic causes. The advent of gene therapy, particularly through antisense oligonucleotides (ASOs), offers a promising avenue toward targeted therapeutic interventions. ASOs by virtue of their ability to modulate gene expression at the mRNA level represent a sophisticated approach to counteract the effects of pathogenic mutations. This review delves into the recent advancements in ASO technology, highlighting its application in preclinical and clinical settings for DEEs. We present evidence of the efficacy of ASOs in ameliorating disease phenotypes in vitro and in vivo, alongside promising outcomes from ongoing clinical trials. The therapeutic landscape for DEEs is on the cusp of significant transformation, underscored by the potential of ASOs to offer precise, personalized, treatments that extend beyond symptomatic relief to potentially rectify the genetic underpinnings of these disorders.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612882","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":"Static and Dynamic Functional Network Connectivity in Parkinson's Disease Patients With Postural Instability and Gait Disorder","authors":"Bo Shen,&nbsp;Qun Yao,&nbsp;Yixuan Zhang,&nbsp;Yinyin Jiang,&nbsp;Yaxi Wang,&nbsp;Xu Jiang,&nbsp;Yang Zhao,&nbsp;Haiying Zhang,&nbsp;Shuangshuang Dong,&nbsp;Dongfeng Li,&nbsp;Yaning Chen,&nbsp;Yang Pan,&nbsp;Jun Yan,&nbsp;Feng Han,&nbsp;Shengrong Li,&nbsp;Qi Zhu,&nbsp;Daoqiang Zhang,&nbsp;Li Zhang,&nbsp;Yun-cheng Wu","doi":"10.1111/cns.70115","DOIUrl":"10.1111/cns.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The exact cause of the parkinsonism gait remains uncertain. We first focus on understanding the underlying neurological reasons for these symptoms through the examination of both static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 64 postural instability and gait disorder-dominated Parkinson's disease (PIGD-PD) patients, 31 non-PIGD-PD (nPIGD-PD) patients, and 54 healthy controls (HC) from Nanjing Brain Hospital. The GIFT software identified five distinct independent components: the basal ganglia (BG), cerebellum (CB), sensory networks (SMN), default mode network (DMN), and central executive network (CEN). We conducted a comparison between the SFNC and DFNC of the five networks and analyzed their correlations with postural instability and gait disorder (PIGD) symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with nPIGD-PD patients, the PIGD-PD patients demonstrated reduced connectivity between CEN and DMN while spending less mean dwell time (MDT) in state 4. This is characterized by strong connections. Compared with HC, PIGD-PD patients exhibited enhanced connectivity in the SFNC between CB and CEN, as well as the network between CB and DMN. Patients with PIGD-PD spent more MDT in state 1, which is characterized by few connections, and less MDT in state 4. In state 3, there was an increase in the functional connectivity between the CB and DMN in patients with PIGD-PD. The nPIGD patients showed increased SFNC connectivity between CB and DMN compared to HC. These patients spent more MDT in state 1 and less in state 4. The MDT and fractional windows of state 2 showed a positive link with PIGD scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Patients with PIGD-PD exhibit a higher likelihood of experiencing reduced brain connectivity and impaired information processing. The enhanced connection between the cerebellum and DMN networks is considered a type of dynamic compensation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612899","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}