CNS Neuroscience & Therapeutics最新文献

{"title":"Decreased cold-inducible RNA-binding protein (CIRP) binding to GluRl on neuronal membranes mediates memory impairment resulting from prolonged hypobaric hypoxia exposure","authors":"Hui Jiang,&nbsp;Chenyan Lu,&nbsp;Haoyang Wu,&nbsp;Jie Ding,&nbsp;Jiayan Li,&nbsp;Jianfeng Ding,&nbsp;Yuqi Gao,&nbsp;Guohua Wang,&nbsp;Qianqian Luo","doi":"10.1111/cns.70059","DOIUrl":"10.1111/cns.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate the molecular mechanisms underlying memory impairment induced by high-altitude (HA) hypoxia, specifically focusing on the role of cold-inducible RNA-binding protein (CIRP) in regulating the AMPA receptor subunit GluR1 and its potential as a therapeutic target.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A mouse model was exposed to 14 days of hypobaric hypoxia (HH), simulating conditions at an altitude of 6000 m. Behavioral tests were conducted to evaluate memory function. The expression, distribution, and interaction of CIRP with GluR1 in neuronal cells were analyzed. The binding of CIRP to <i>GluR1</i> mRNA and its impact on GluR1 protein expression were examined. Additionally, the role of CIRP in GluR1 regulation was assessed using <i>Cirp</i> knockout mice. The efficacy of the Tat-C16 peptide, which consists of the Tat sequence combined with the CIRP 110-125 amino acid sequence, was also tested for its ability to mitigate HH-induced memory decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CIRP was primarily localized in neurons, with its expression significantly reduced following HH exposure. This reduction was associated with decreased GluR1 protein expression on the cell membrane and increased localization in the cytoplasm. The interaction between CIRP and GluR1 was diminished under HH conditions, leading to reduced GluR1 stability on the cell membrane and increased cytoplasmic relocation. These changes resulted in a decreased number of synapses and dendritic spines, impairing learning and memory functions. Administration of the Tat-C16 peptide effectively ameliorated these impairments by modulating GluR1 expression and distribution in HH-exposed mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CIRP plays a critical role in maintaining synaptic integrity under hypoxic conditions by regulating GluR1 expression and distribution. The Tat-C16 peptide shows promise as a therapeutic strategy for alleviating cognitive decline associated with HA hypoxia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306778","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":"Expression of microRNA induced by postoperative delirium-like behavior is associated with long-term default mode network disruption: Sequencing and a secondary analysis of resting-state fMRI data","authors":"Yang Liu,&nbsp;Huiru Feng,&nbsp;Huiqun Fu,&nbsp;Binbin Nie,&nbsp;Tianlong Wang","doi":"10.1111/cns.70038","DOIUrl":"https://doi.org/10.1111/cns.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Resting state functional magnetic resonance imaging (rs-fMRI) has been widely used in studying default mode network (DMN) changes in postoperative delirium (POD). Reproducibility and interpretability of the analyzing results remain insufficiently studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Delirium-like behavior was induced by tibial fixation surgery under isoflurane anesthesia. Firstly, we evaluated delirium-like behavior and inflammatory responses in hippocampus and systemic level. Then the expressions of microRNA (miRNA) and target gene were sequenced and validated. Afterwards the functional connectivity (FC) in DMN was analyzed. Finally, results were correlated with DMN changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>POD-like behavior caused significant changes of miR-34b-5p, miR-328-5p, and miR-3505 in miRNA level and <i>Nos1</i>, <i>Tubb3</i>, and <i>Gys1</i> in the gene level. The FC in left and right hippocampus (L-Hip and R-Hip) and right auditory cortex (R-AC) was found significantly changed. Significant correlations were found in FC_L-Hip/R-AC and FC_R-Hip/R-AC for miR-34b-5p and miR-3505, as well as <i>Nos1</i> and <i>Tubb3</i>. For miR-328-5p, no significant correlations were found.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study demonstrates that POD-like behavior induced significant miRNA and gene expression changes were associated with hippocampus related long-term FC disruption in DMN. The results increased reproducibility and interpretability for standardized rs-fMRI data analysis, as well as providing potential targets for postoperative delirium treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316681","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":"Early screening of post-stroke fall risk: A simultaneous multimodal fNIRs-EMG study","authors":"Zheng Yang,&nbsp;Liu Ye,&nbsp;Lining Yang,&nbsp;Qiuyi Lu,&nbsp;Anqi Yu,&nbsp;Dingqun Bai","doi":"10.1111/cns.70041","DOIUrl":"10.1111/cns.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Stroke is the third-leading cause of death and disability, and poststroke falls (PSF) are common at all stages after stroke and could even lead to injuries or death. Brain information from functional near-infrared spectroscopy (fNIRs) may precede conventional imaging and clinical symptoms but has not been systematically considered in PSF risk prediction. This study investigated the difference in brain activation between stroke patients and healthy subjects, and this study was aimed to explore fNIRs biomarkers for early screening of PSF risk by comparing the brain activation in patients at and not at PSF risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we explored the differences in brain activation and connectivity between stroke and healthy subjects by synchronizing the detection of fNIRs and EMG tests during simple (usual sit-to-stand) and difficult tasks (sit-to-stand based on EMG feedback). Thereby further screened for neuroimaging biomarkers for early prediction of PSF risk by comparing brain activation variability in poststroke patients at and not at fall risk during simple and difficult tasks. The area under the ROC curve (AUROC), sensitivity, and specificity were used to compare the diagnostic effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 40 patients (22 not at and 18 at PSF risk) and 38 healthy subjects were enrolled. As the difficulty of standing task increased, stroke patients compared with healthy subjects further increased the activation of the unaffected side of supplementary motor area (H-SMA) and dorsolateral prefrontal cortex-Brodmann area 46 (H-DLFC-BA46) but were unable to increase functional connectivity (Group*Task: <i>p</i> &lt; 0.05). More importantly, the novel finding showed that hyperactivation of the H-SMA during a simple standing task was a valid fNIRs predictor of PSF risk [AUROC 0.74, <i>p</i> = 0.010, sensitivity 77.8%, specificity 63.6%].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provided novel evidence that fNIR-derived biomarkers could early predict PSF risk that can facilitate the widespread use of real-time assessment tools in early screening and rehabilitation. Meanwhile, this study demonstrated that the higher brain activation and inability to increase the brain functional connectivity in stroke patients during difficult task indicated the inefficient use of brain resources.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306782","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 hypothalamus-lateral periaqueductal gray GABAergic neural projection facilitates arousal following sevoflurane anesthesia in mice","authors":"Dan Wang,&nbsp;Chang Bao,&nbsp;Huimin Wu,&nbsp;Jiannan Li,&nbsp;Xinxin Zhang,&nbsp;Sa Wang,&nbsp;Fang Zhou,&nbsp;Huiming Li,&nbsp;Hailong Dong","doi":"10.1111/cns.70047","DOIUrl":"https://doi.org/10.1111/cns.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The lateral hypothalamus (LHA) is an evolutionarily conserved structure that regulates basic functions of an organism, particularly wakefulness. To clarify the function of LHA^GABA neurons and their projections on regulating general anesthesia is crucial for understanding the excitatory and inhibitory effects of anesthetics on the brain. The aim of the present study is to investigate whether LHA^GABA neurons play either an inhibitory or a facilitatory role in sevoflurane-induced anesthetic arousal regulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used fiber photometry and immunofluorescence staining to monitor changes in neuronal activity during sevoflurane anesthesia. Opto-/chemogenetic modulations were employed to study the effect of neurocircuit modulations during the anesthesia. Anterograde tracing was used to identify a GABAergic projection from the LHA to a periaqueductal gray (PAG) subregion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>c-Fos staining showed that LHA^GABA activity was inhibited by induction of sevoflurane anesthesia. Anterograde tracing revealed that LHA^GABA neurons project to multiple arousal-associated brain areas, with the lateral periaqueductal gray (LPAG) being one of the dense projection areas. Optogenetic experiments showed that activation of LHA^GABA neurons and their downstream target LPAG reduced the burst suppression ratio (BSR) during continuous sevoflurane anesthesia. Chemogenetic experiments showed that activation of LHA^GABA and its projection to LPAG neurons prolonged the anesthetic induction time and promoted wakefulness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, we show that an inhibitory projection from LHA^GABA to LPAG^GABA neurons promotes arousal from sevoflurane-induced loss of consciousness, suggesting a complex control of wakefulness through intimate interactions between long-range connections.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316680","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 novel strategy for spinal cord reconstruction via vascularized allogeneic spinal cord transplantation combine spinal cord fusion","authors":"Weihua Zhang,&nbsp;Rongyu Lan,&nbsp;Tingting Shen,&nbsp;Jie Qin,&nbsp;Zhihui Wang,&nbsp;Jiayang Chen,&nbsp;Jiaxing Wang,&nbsp;Zhuotan Wu,&nbsp;Yudong Xu,&nbsp;Yangyang Shen,&nbsp;Qikai Lin,&nbsp;Yuan Chen,&nbsp;Yi Wei,&nbsp;Yiwen Liu,&nbsp;Yuance Ning,&nbsp;Yiyan Zhou,&nbsp;Liji Deng,&nbsp;Linxuan Han,&nbsp;Xiaofei Wu,&nbsp;Haixuan Deng,&nbsp;Zhenbin Cao,&nbsp;Xianping Yao,&nbsp;Xiaoping Ren","doi":"10.1111/cns.70020","DOIUrl":"10.1111/cns.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Spinal cord injuries (SCI) pose persistent challenges in clinical practice due to the secondary injury. Drawing from our experience in spinal cord fusion (SCF), we propose vascularized allogeneic spinal cord transplantation (vASCT) as a novel approach for SCI, much like organ transplantation has revolutionized organ failure treatment and vascularized composite-tissue allotransplantation has addressed limb defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this study, 24 dogs were paired and underwent vASCT, with donor spinal cord grafts and polyethylene glycol (PEG) application for SCF. The experimental group (<i>n</i> = 8) received tacrolimus and methylprednisolone, while the control group (<i>n</i> = 4) received only methylprednisolone. Safety and efficacy of vASCT were evaluated through electrophysiology, imaging, and 6-month follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The experimental group showed substantial recovery in hind limb motor function. Imaging revealed robust survival of spinal cord grafts and restoration of spinal cord continuity. In contrast, the control group maintained hind limb paralysis, with imaging confirming spinal cord graft necrosis and extensive defects. Electrophysiologically, the experimental group exhibited restored motor evoked potential signal conduction postoperatively, unlike the control group. Notably, PEG application during vASCT led to signal conduction recovery in intraoperative spinal cord evoked potential examinations for all dogs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In the vASCT surgical model, the combination of PEG with tacrolimus has demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. Notably, a low dose of tacrolimus has also exhibited an excellent anti-immune rejection effect. These findings highlight vASCT's potential promise as a therapeutic strategy for addressing irreversible SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306777","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":"KA-mediated excitotoxicity induces neuronal ferroptosis through activation of ferritinophagy","authors":"Yi-Yue Jiang,&nbsp;Wei-Long Wu,&nbsp;Jia-Ni Huang,&nbsp;Na Liu,&nbsp;Jing Wang,&nbsp;Xiao-Rui Wan,&nbsp;Zheng-Hong Qin,&nbsp;Yan Wang","doi":"10.1111/cns.70054","DOIUrl":"10.1111/cns.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aims to elucidate the role of Fe²⁺ overload in kainic acid (KA)-induced excitotoxicity, investigate the involvement of ferritinophagy selective cargo receptor NCOA4 in the pathogenesis of excitotoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Western blotting was used to detect the expression of FTH1, NCOA4, Lamp2, TfR, FPN, and DMT1 after KA stereotaxic injection into the unilateral striatum of mice. Colocalization of Fe²⁺ with lysosomes in KA-treated primary cortical neurons was observed by using confocal microscopy. Desferrioxamine (DFO) was added to chelate free iron, a CCK8 kit was used to measure cell viability, and the Fe²⁺ levels were detected by FerroOrange. BODIPY C11 was used to determine intracellular lipid reactive oxygen species (ROS) levels, and the mRNA levels of PTGS2, a biomarker of ferroptosis, were measured by fluorescent quantitative PCR. 3-Methyladenine (3-MA) was employed to inhibit KA-induced activation of autophagy, and changes in ferritinophagy-related protein expression and the indicated biomarkers of ferroptosis were detected. Endogenous NCOA4 was knocked down by lentivirus transfection, and cell viability and intracellular Fe²⁺ levels were observed after KA treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Western blot results showed that the expression of NCOA4, DMT1, and Lamp2 was significantly upregulated, while FTH1 was downregulated, but there were no significant changes in TfR and FPN. The fluorescence results indicated that KA enhanced the colocalization of free Fe²⁺ with lysosomes in neurons. DFO intervention could effectively rescue cell damage, reduce intracellular lipid peroxidation, and decrease the increased transcript levels of PTGS2 caused by KA. Pretreatment with 3-MA effectively reversed KA-induced ferritinophagy and ferroptosis. Endogenous interference with NCOA4 significantly improved cell viability and reduced intracellular free Fe²⁺ levels in KA-treated cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>KA-induced excitotoxicity activates ferritinophagy, and targeting ferritinophagy effectively inhibits downstream ferroptosis. Interference with NCOA4 effectively attenuates KA-induced neuronal damage. This study provides a potential therapeutic target for excitotoxicity related disease conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277589","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 β-sitosterol on anxiety in migraine-induced rats: The role of oxidative/nitrosative stress and mitochondrial function","authors":"Ali Vafaei,&nbsp;Ahmad Vafaeian,&nbsp;Arad Iranmehr,&nbsp;Ehsan Nassireslami,&nbsp;Behnam Hasannezhad,&nbsp;Yasaman Hosseini","doi":"10.1111/cns.14892","DOIUrl":"https://doi.org/10.1111/cns.14892","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Anxiety often coexists with migraine, and both conditions share a commonality in oxidative/nitrosative stress and mitochondrial dysfunction contributing to their pathogenesis. β-Sitosterol, a plant sterol, has shown promise in mitigating oxidative/nitrosative stress, enhancing mitochondrial function, and exerting neuroprotective effects. In this study, we investigated the impact of β-sitosterol on migraine-associated anxiety and whether this effect was associated with alleviation of oxidative/nitrosative stress and improvement in mitochondrial function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nitroglycerin was used to induce migraine in adult male Wistar rats. β-Sitosterol treatment consisted of daily intraperitoneal injections (10 mg/kg) for 10 days following migraine induction. Anxiety levels were evaluated using open-field test (OFT) and hole-board test (HBT). Frontal cortex samples were analyzed for malondialdehyde (MDA), glutathione (GSH), reactive oxygen/nitrogen species, nitric oxide (NO) (markers of oxidative/nitrosative stress), and ATP (indicator of mitochondrial function).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Migraine induction led to impaired performance in both the OFT and the HBT. Concurrently, it elevated MDA, reactive oxygen/nitrogen species, and NO levels while diminishing GSH levels in the frontal cortex, signifying heightened oxidative/nitrosative stress. Moreover, ATP levels decreased, indicating mitochondrial dysfunction. Treatment with β-sitosterol significantly restored performance in both behavioral assays and normalized the levels of MDA, GSH, reactive oxygen/nitrogen species, NO, and ATP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>β-Sitosterol exerted anxiolytic effects in migraine, which can be attributed to its ability to ameliorate oxidative/nitrosative stress and enhance mitochondrial function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273269","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":"Changes of NLRP3 in serum and cerebrospinal fluid of patients after moderate to severe traumatic brain injury and their predictive values for prognosis","authors":"Wei Chen,&nbsp;Zhigang Wang,&nbsp;Gengfan Ye,&nbsp;Guangyao Zhu,&nbsp;Shiwei Li,&nbsp;Pandi Chen,&nbsp;Hongcai Wang,&nbsp;Shufeng Zou,&nbsp;Maosong Chen","doi":"10.1111/cns.70009","DOIUrl":"https://doi.org/10.1111/cns.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) remains a major concern for global health. Recent studies have suggested the role of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an inflammatory marker, in the cerebrospinal fluid (CSF) and serum as potential indicators of TBI prognosis. The objective of the study was to characterize NLRP3 as a clinically applicable tool for predicting the outcomes of TBI patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 270 patients with moderate to severe TBI were included in this retrospective analysis. Serum and CSF samples were collected at 1-, 3-, 7-, and 21-day post-injury to measure NLRP3 levels. The prognosis of patients was evaluated after 3 months using the Glasgow Outcome Scale (GOS). Patients were categorized into good prognosis (GOS score &gt;3) and poor prognosis (GOS score ≤3) groups. The relationship between NLRP3 levels and prognosis was analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with poor prognosis had significantly elevated NLRP3 levels in their serum on days 1 and 3 post-injury compared with those with a good prognosis. The difference was more pronounced during these early days compared with days 7 and 21. However, NLRP3 levels in CSF consistently showed a large difference between the two groups throughout the observation period. Receiver operating characteristic analysis revealed that the level of NLRP3 in the CSF on day 3 post-injury had the highest predictive value for prognosis, with an area under the curve of 0.83, followed by the level of NLRP3 in the serum on day 3 post-injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The levels of NLRP3, especially in the CSF on day 3 post-injury, can serve as a potential biomarker for predicting prognosis in moderate to severe TBI patients. Early measurement of NLRP3 levels can provide valuable insights into patient outcomes and guide therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273268","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":"Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease","authors":"Feifei Zang,&nbsp;Xinyi Liu,&nbsp;Dandan Fan,&nbsp;Cancan He,&nbsp;Zhijun Zhang,&nbsp;Chunming Xie,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative,&nbsp;for the Alzheimer's Disease Metabolomics Consortium","doi":"10.1111/cns.70029","DOIUrl":"https://doi.org/10.1111/cns.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid metabolism-related factors across the Alzheimer's disease (AD) spectrum populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from 242 AD spectrum subjects, including biological, neuroimaging, and general cognition, were obtained from the Alzheimer's Disease Neuroimaging Initiative for this cross-sectional study. The study utilized a sliding-window approach to assess whole-brain dFNC, investigating group differences and associations with biological and cognitive factors. Abnormal dFNC was used in the classification of AD spectrum populations by support vector machine. Mediation analysis was performed to explore the relationships between lipid-related indicators, dFNC, cerebrospinal fluid (CSF) biomarkers, and cognitive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant group difference concerning were observed in relation to <i>APOE</i>-ε4 status, CSF biomarkers, and cognitive scores. Two reoccurring connectivity states were identified: state-1 characterized by frequent but weak connections, and state-II characterized by less frequent but strong connections. Pre-AD subjects exhibited a preference for spending more time in state-I, whereas AD patients tended remain in state-II for longer periods. Group difference in dFNC was primarily found between AD and non-AD participants within each state. The dFNC of state-I yielded strong power to distinguish AD from other groups compared with state-II. <i>APOE</i>-ε4⁺, high polygenic score, and high serum lipid group were strongly associated with network disruption between association cortex system and sensory cortex system that characterized elevation of cognitive function, which may suggest a compensatory mechanism of dFNC in state-I, whereas differential connections of state-II mediated the relationships between <i>APOE</i>-ε4 genotype and CSF biomarkers, and cognitive indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The dysfunction of dFNC temporal–spatial patterns and increased cognition in individuals with <i>APOE</i>-ε4, high polygenic score, and higher serum lipid levels shed light on the lipid-related mechanisms of dynamic network reorganization in AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275035","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":"Changes in the medial prefrontal cortex metabolites after 6 months of medication therapy for patients with bipolar disorder: A 1H-MRS study","authors":"Haijin Li,&nbsp;Ju Gao,&nbsp;Huihui Song,&nbsp;Xuna Yang,&nbsp;Cai Li,&nbsp;Yue Zhang,&nbsp;Jiahui Wang,&nbsp;Yitong Liu,&nbsp;Dong Wang,&nbsp;Hong Li","doi":"10.1111/cns.70048","DOIUrl":"https://doi.org/10.1111/cns.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The study aimed to assess brain metabolite differences in the medial prefrontal cortex (mPFC) between acute and euthymic episodes of bipolar disorder (BD) with both mania and depression over a 6-month medication treatment period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilized ¹H-MRS technology to assess the metabolite levels in 53 individuals with BD (32 in depressive phase, 21 in manic phase) and 34 healthy controls (HCs) at baseline. After 6 months of medication treatment, 40 subjects underwent a follow-up scan in euthymic state. Metabolite levels, including N-acetyl aspartate (NAA), glutamate (Glu), and Glutamine (Gln), were measured in the mPFC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients experiencing depressive and manic episodes exhibited a notable reduction in NAA/Cr + PCr ratios at baseline compared to healthy controls (<i>p</i> = 0.004; <i>p</i> = 0.006) in baseline, compared with HCs. Over the 6-month follow-up period, the manic group displayed a significant decrease in Gln/Cr + PCr compared to the initial acute phase (<i>p</i> = 0.03). No significant alterations were found in depressed group between baseline and follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study suggests that NAA/Cr + PCr ratios and Gln/Cr + PCr ratios in the mPFC may be associated with manic and depressive episodes, implicating that Gln and NAA might be useful biomarkers for distinguishing mood phases in BD and elucidating its mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273157","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}