CNS Neuroscience & Therapeutics最新文献

{"title":"The Restoration of Energy Pathways Indicates the Efficacy of Ketamine Treatment in Depression: A Metabolomic Analysis","authors":"Zerui You,&nbsp;Xiaofeng Lan,&nbsp;Chengyu Wang,&nbsp;Haiying Liu,&nbsp;Weicheng Li,&nbsp;Siming Mai,&nbsp;Haiyan Liu,&nbsp;Fan Zhang,&nbsp;Guanxi Liu,&nbsp;Xiaoyu Chen,&nbsp;Yanxiang Ye,&nbsp;Yanling Zhou,&nbsp;Yuping Ning","doi":"10.1111/cns.70324","DOIUrl":"https://doi.org/10.1111/cns.70324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Despite the clinical benefits of ketamine in treating major depressive disorder (MDD), some patients exhibit drug resistance, and the intricate mechanisms underlying this await comprehensive explication. We used metabolomics to find biomarkers for ketamine efficacy and uncover its mechanisms of action.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 40 MDD patients treated with ketamine in the discovery cohort and 24 patients in the validation cohort. Serum samples from the discovery cohort receiving ketamine were analyzed using ultra performance liquid chromatography-mass spectrometry to study metabolomic changes and identify potential biomarkers. Metabolic alterations were evaluated pre- and post-ketamine treatment. Spearman correlation was applied to examine the relationship between metabolite alterations and depressive symptom changes. In addition, potential biomarkers, particularly thyroxine, were investigated through quantitative measurements in the validation cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that energy metabolite changes (adenosine triphosphate, adenosine diphosphate [ADP], pyruvate) were different in responders versus non-responders. The magnitude of the ADP shift was strongly correlated with the rate of reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores (Rho = 0.48, <i>p</i>_FDR = 0.018). Additionally, baseline free triiodothyronine (FT3) levels are inversely associated with the rate of MADRS reduction (Rho = −0.645, <i>p</i> = 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Ketamine ameliorates depressive symptoms by modulating metabolic pathways linked to energy metabolism. Low baseline FT3 levels appear to predict a positive response in MDD patients, suggesting FT3 has potential as a biological marker for clinical ketamine treatment.</p>\u0000 \u0000 <p><b>Trial Registration:</b> ChiCTR-OOC-17012239</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581636","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":"Neural Correlates and Adaptive Mechanisms in Vascular Cognitive Impairment: Exploration of a Structure–Function Coupling Network","authors":"Jing Jin,&nbsp;Jie Ma,&nbsp;Jia-Jia Wu,&nbsp;Juan-Juan Lu,&nbsp;Hao-Yu Lu,&nbsp;Mou-Xiong Zheng,&nbsp;Xu-Yun Hua,&nbsp;Jian-Guang Xu","doi":"10.1111/cns.70205","DOIUrl":"https://doi.org/10.1111/cns.70205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebral small vessel disease exacerbates cognitive decline, yet the structural–functional coupling mechanisms in vascular cognitive impairment (VCI) remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 121 participants, with 68 individuals with VCI and 53 healthy controls. Participants underwent neuropsychological assessments and multimodal imaging. We compared white matter integrity, structural network topology, and functional network topology between groups, exploring the relationship between structure–function coupling and cognitive function. Family-wise error (FWE) correction was applied to account for multiple comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>VCI participants showed reduced fractional anisotropy and increased mean and radial diffusivity in white matter. Structural network analysis revealed lower global and local efficiency, reduced small-world properties, and increased characteristic path length. Nodal properties, particularly in key regions of the default mode and visual networks, were significantly altered in VCI participants. While no significant differences were observed in functional network topology, VCI participants exhibited enhanced structure–function coupling in critical nodes of the default mode and visual networks. This enhancement correlated with memory function and information processing speed in the temporal calcarine, insula, occipital, and lingual regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study identifies disrupted brain networks and enhanced compensatory mechanisms in VCI, offering insights into neuroplasticity in VCI and contributing to dementia prevention strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581639","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":"CPCGI Alleviates Neural Damage by Modulating Microglial Pyroptosis After Traumatic Brain Injury","authors":"Lu-Lu Yu,&nbsp;Lei Sun,&nbsp;Ting-Ting Yu,&nbsp;An-Chen Guo,&nbsp;Jian-Ping Wu,&nbsp;Jun-Min Chen,&nbsp;Qun Wang","doi":"10.1111/cns.70322","DOIUrl":"https://doi.org/10.1111/cns.70322","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) is a major global cause of mortality and long-term disability, with limited therapeutic options. Microglial pyroptosis, a form of programmed cell death associated with inflammation, has been implicated in exacerbating neuroinflammation and secondary injury following TBI. Compound porcine cerebroside ganglioside injection (CPCGI) has shown anti-inflammatory and antioxidant properties, but its effects on pyroptosis remain unexplored. This study investigates the role of CPCGI in TBI and its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A controlled cortical impact (CCI) model was utilized to establish TBI in vivo, while lipopolysaccharide (LPS) was used in vitro to induce microglial activation that mimicked TBI conditions. The effects of CPCGI on microglial pyroptosis and inflammatory cytokines were analyzed through immunofluorescence, flow cytometry, western blotting, and quantitative real-time PCR (qRT-PCR). The involvement of the NLRP3 inflammasome in CPCGI's mechanism was examined using NLRP3 overexpression or the NLRP3 agonist BMS-986299. A microglia–neuron interaction model was created, and neuronal injury was assessed with the Cell Counting Kit-8 and Fluoro-Jade C (FJC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with CPCGI resulted in significant improvement in the neurobehavioral outcomes, reduced lesion volume, and decreased neuronal loss following TBI. Notably, TBI induced microglial pyroptosis and the release of pro-inflammatory cytokines, while CPCGI inhibited microglial pyroptosis, thereby mitigating the inflammatory response and reducing neuronal damage. Mechanistically, overexpression of NLRP3 in microglial cells reversed the inhibitory effects of CPCGI on microglial pyroptosis, indicating that CPCGI's inhibition of microglial pyroptosis may be mediated by the NLRP3 inflammasome. Furthermore, NLRP3 overexpression or administration of the NLRP3 agonist BMS-986299 negated the neuroprotective effects of CPCGI in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that CPCGI provides neuroprotection in TBI by targeting NLRP3 inflammasome-mediated microglial pyroptosis, thereby improving the neuroinflammatory microenvironment and promoting neurological recovery. This underscores its potential as a promising candidate for TBI treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581638","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":"Causal Association Between Major Depressive Disorder and Cortical Structure: A Bidirectional Mendelian Randomization Study and Mediation Analysis","authors":"Hui Zheng,&nbsp;Yong-Jiang Fang,&nbsp;Xiao-Ying Wang,&nbsp;Si-Jia Feng,&nbsp;Tai-Chun Tang,&nbsp;Min Chen","doi":"10.1111/cns.70319","DOIUrl":"https://doi.org/10.1111/cns.70319","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous observational studies have reported a possible association between major depressive disorder (MDD) and abnormal cortical structure. However, it is unclear whether MDD causes reductions in global cortical thickness (CT) and global area (SA). Objective: We aimed to test the bidirectional causal relationship between MDD and CT and SA using a Mendelian randomization (MR) design and performed exploratory analyses of MDD on CT and SA in different brain regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Summary-level data were obtained from two GWAS meta-analysis studies: one screening for single nucleotide polymorphisms (SNPs) predicting the development of MDD (<i>n</i> = 135,458) and the other identifying SNPs predicting the magnitude of cortical thickness (CT) and surface area (SA) (<i>n</i> = 51,665).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that MDD caused a decrease in CT in the medial orbitofrontal region, a decrease in SA in the paracentral region, and an increase in SA in the lateral occipital region. C-reactive protein, tumor necrosis factor alpha (TNF-α), interleukin-1β, and interleukin-6 did not mediate the reduction. We also found that a reduction in CT in the precentral region and a reduction in SA in the orbitofrontal regions might be associated with a higher risk of MDD. Conclusion: Our study did not suggest an association between MDD and cortical CT and SA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581640","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":"Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease","authors":"Jianhui Su,&nbsp;Lanyang Zhao,&nbsp;Runze Fu,&nbsp;Zhe Tang","doi":"10.1111/cns.70329","DOIUrl":"https://doi.org/10.1111/cns.70329","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is characterized by a decline in cognitive, learning, and memory abilities. Neuroinflammation is associated with the spread of tau tangles in the neocortex of AD, leading to cognitive impairment. Therefore, clarifying the pathogenesis of Neuroinflammation and finding effective treatments are the crucial issues for the clinical management of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We systematically review the latest research on the pathogenesis and therapeutic strategies of AD in PubMed, Web of Science, and Elsevier SD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>In this review, the mechanism of the effect of gut-brain axis lipid metabolism mediated by circadian rhythm on AD was discussed, and we also analysed the effects of inflammation and endoplasmic reticulum stress (ERS) induced by lipid abnormalities on intestinal mucosal barrier and neurodegeneration; furthermore, the importance of lipid homeostasis (phospholipids, fatty acids, sterol) in maintaining the functions of endoplasmic reticulum was emphasized. Meanwhile, as lipid composition affects protein conformation, the membrane phospholipids surrounding sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) that influence SERCA to release Ca²⁺ mediating inflammation were also reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We interpreted the mechanism of action between lipid microdomains and ER membrane proteins, reviewed the role of the new pathway of circadian rhythm, lipid metabolism, intestinal mucosa, and brain signaling in the pathogenesis of AD, and proposed strategies to prevent AD by changing the dietary lipid measures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581637","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":"Akkermansia muciniphila Modulates Central Nervous System Autoimmune Response and Cognitive Impairment by Inhibiting Hippocampal NLRP3-Mediated Neuroinflammation","authors":"Xiaobing Li,&nbsp;Dengna Lin,&nbsp;Xin Hu,&nbsp;Xiongwei Shi,&nbsp;Wenxuan Huang,&nbsp;Yi Ouyang,&nbsp;Xiaohong Chen,&nbsp;Yingqiong Xiong,&nbsp;Xiaomu Wu,&nbsp;Daojun Hong,&nbsp;Hao Chen","doi":"10.1111/cns.70320","DOIUrl":"https://doi.org/10.1111/cns.70320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Numerous studies have demonstrated the significant role of <i>Akkermansia muciniphila</i> (<i>A. muciniphila</i>) in enhancing host immune responses and metabolic functions. However, its increased presence in multiple sclerosis (MS) patients has led to a focus on the relationships between <i>A. muciniphila</i> and diseases, with the underlying mechanisms remaining unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Solochrome cyanin, hematoxylin–eosin staining (H&amp;E) and immunofluorescence staining were used to assess demyelination and inflammation. Gut microbiota changes were examined by 16S rRNA sequencing. Intracellular cytokine levels were assessed by flow cytometry. Cognitive impairment was evaluated using four behavioral tests. Intestinal barrier function and pyrin domain-containing protein 3 (NLRP3)-mediated neuroinflammation were evaluated by immunoblotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that treatment with an appropriate dose of <i>A. muciniphila</i> (5.0 × 10⁷ CFU/mL) reduced neuropathology and disease severity in experimental autoimmune encephalomyelitis (EAE) mice. In addition, <i>A. muciniphila</i> supplementation increased the diversity and abundance of intestinal microbiota while decreasing the <i>Firmicutes/Bacteroidetes</i> ratio. Moreover, it improved intestinal barrier function and attenuated Th17 responses in the gut, central nervous system (CNS), and lymphoid tissues, without affecting Treg response in the lymphoid tissue. Furthermore, <i>A. muciniphila</i> administration partly regulated cognitive impairment and hippocampal NLRP3-mediated neuroinflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest that <i>A. muciniphila</i> holds promise as a probiotic for treating NLRP3-associated inflammatory disorders and cognitive impairment, including MS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565100","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":"DNLA Delayed the Appearance of Learning and Memory Impairment of APP/PS1 Mice: Involvement of mTOR/TFEB/v-ATPase Signaling Pathway","authors":"Yajuan Wu,&nbsp;Xuejia Liu,&nbsp;Guohui Luo,&nbsp;Qiye Li,&nbsp;Bin Guo,&nbsp;Lisheng Li,&nbsp;Jing Nie","doi":"10.1111/cns.70300","DOIUrl":"https://doi.org/10.1111/cns.70300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cognitive impairment that currently is incurable. There is existing evidence to suggest that vacuolar adenosine triphosphatase (v-ATPase) is one of the early key driving factors in the pathological process of AD. Thus, early intervention of v-ATPase may be a viable strategy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Observing whether early intervention with DNLA can delay learning and memory impairment in mice, and further exploring the mechanism of DNLA delaying AD in vitro based on v-ATPase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four-month-old APP/PS1 transgenic mice were treated with alkaloids from Dendrobium nobile Lindl (DNLA) 20 and 40 mg/kg/day for 5 months. The Morris water maze test and nest test showed that DNLA administration significantly delayed the appearance of cognitive deficits in APP/PS1 mice. We further investigated the mechanism of DNLA promoting lysosome acidification in vitro by using PC12 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that DNLA increases the degradation of β-amyloid (Aβ) contained in the autophagic lysosomes and alleviates the aging of neurons by promoting lysosome acidification and improving autophagy flow. In PC12 cells, DDB could promote the separation of mTOR and lysosome, promote the nuclear translocation of transcription factor EB (TFEB), and then promote lysosome biogenesis and lysosome acidification by targeting ATP6V1A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results unraveled that preventive administration of DNLA may delay the impairment of learning and memory in APP/PS1 mice. The molecular mechanism may be related to promoting the mTOR-TFEB-v-ATPase pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554856","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":"Central Thalamic Deep Brain Stimulation Modulates Autonomic Nervous System Responsiveness in Disorders of Consciousness","authors":"Tianqing Cao,&nbsp;Xiaoke Chai,&nbsp;Hongbin Wu,&nbsp;Nan Wang,&nbsp;Jiuxiang Song,&nbsp;Qiheng He,&nbsp;Sipeng Zhu,&nbsp;Yitong Jia,&nbsp;Yi Yang,&nbsp;Jizong Zhao","doi":"10.1111/cns.70274","DOIUrl":"https://doi.org/10.1111/cns.70274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The heart rate variability (HRV) of patients with disorders of consciousness (DOC) differs from healthy individuals. However, there is rarely research on HRV among DOC patients following treatment with deep brain stimulation (DBS). This study aims to investigate the modulatory effects of DBS-on the central-autonomic nervous system of DOC based on the study of HRV variations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted DBS surgery on eight patients with DOC. Postoperatively, all patients underwent short-duration stimulation for 3 days, with stimulation frequencies of 25 Hz, 50 Hz, and 100 Hz respectively. Each day comprised four cycles, with a stimulation duration of 30 min DBS-on and 90 min DBS-off. We obtained the coma recovery scale-revised (CRS-R) scores and synchronously recorded electrocardiographic data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Resulits</h3>\u0000 \u0000 <p>We analyzed the HRV indices, including time-domain and frequency-domain parameters across various time points for all patients. The HRV exhibited a consistent trend across the three groups with different parameters. Notably, the most pronounced HRV changes were induced by the 100 Hz. Long-term follow-up indicates that high-frequency (HF), low-frequency (LF), and total power (TP) of HRV may serve as predictive indicators in the prognosis of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study reveals that DBS enhances DOC patient consciousness while increasing HRV. Specifically, frequency-domain indices correlate with favorable prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565101","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":"Characteristics of Cerebral Autoregulation After Mechanical Thrombectomy and Its Relationship With Prognosis","authors":"Yang Qu,&nbsp;Menglu Cong,&nbsp;Jia Liu,&nbsp;Pan-Deng Zhang,&nbsp;Zi-Duo Shen,&nbsp;Han Zhang,&nbsp;Yingying Sun,&nbsp;Hongjing Zhu,&nbsp;Chao Li,&nbsp;Peng Zhang,&nbsp;Junlei Chang,&nbsp;Kejia Zhang,&nbsp;Jiaxin Ren,&nbsp;Hang Jin,&nbsp;Xin Sun,&nbsp;Yi Yang,&nbsp;Zhen-Ni Guo","doi":"10.1111/cns.70323","DOIUrl":"https://doi.org/10.1111/cns.70323","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the characteristics of dynamic cerebral autoregulation (dCA) in patients after mechanical thrombectomy (MT) and the relationship between dCA and prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective study, 89 and 158 patients were enrolled in the MT and non-MT groups, respectively. Both groups underwent dCA measurements within 3 days after stroke. The transfer function parameter, phase difference (PD), and gain were used to quantify dCA. A favorable outcome was defined as a modified Rankin Scale score ≤ 2 at 90 days. The collateral score was used to reflect the collateral reserve capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MT was associated with better PD in both the affected and unaffected sides. In the MT group, the PD of the affected side was an independent predictor of favorable outcomes (odds ratio [OR] 0.927, 95% confidence interval [CI] 0.885–0.970; <i>p</i> &lt; 0.001). The area under the receiver operating characteristic curve for predicting favorable outcomes of the PD on the affected side was 0.759 (95% CI, 0.654–0.864; <i>p</i> &lt; 0.001). Further, good collaterals were independently associated with better PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MT has a positive effect on dCA during the acute phase of stroke. For patients undergoing MT, dCA is a reliable indicator for predicting prognosis and may be an intervention target to improve outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533593","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":"Exploring the Therapeutic Mechanism of Xinbao Pill in Brain Injury After Cardiopulmonary Resuscitation Based on Network Pharmacology, Metabolomics, and Experimental Verification","authors":"Dongli Li,&nbsp;Qihui Wu,&nbsp;Zunjiang Li,&nbsp;Baijian Chen,&nbsp;Xing Sun,&nbsp;Qiqi Wu,&nbsp;Zhenzhu Ding,&nbsp;Linling Liu,&nbsp;Jiansong Fang,&nbsp;Ruifeng Zeng,&nbsp;Yong Gu,&nbsp;Banghan Ding","doi":"10.1111/cns.70297","DOIUrl":"https://doi.org/10.1111/cns.70297","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Post-cardiopulmonary resuscitation brain injury (PBI) is essentially the cerebral ischemia reperfusion (CIR) injury, which is the main cause of death and long-term disability in patients with cardiac arrest. So far, there is no treatment for PBI; thus, it is urgent to develop new drugs or therapies for the prevention and treatment of brain injury after cardiopulmonary resuscitation. Although multiple constituent herbs or active ingredients of Xinbao Pill (XBP) have shown neuroprotective effects, whether XBP could play a therapeutic role on PBI is still unknown. This study aimed to illustrate the neuroprotective effect of XBP on PBI and probe the underlying mechanisms.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Method&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We first performed the cell and animal experiments to validate the protective effect of XBP on neurological function. We next identified the potential differential metabolites via metabolomics analysis. We further conducted a comprehensive network pharmacology analysis including overlap gene analysis, protein–protein interaction network, and gene–biological process–module function network to preliminarily investigate the specific mechanism of action (MOA) of XBP against PBI. Finally, PCR, MTT, ELISA assay, as well as Western blotting experiments were made to validate our proposed molecular mechanisms.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Result&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The in vitro experiment showed that XBP could increase cell viability and ameliorate cell morphological damage in PC12 cells exposed to oxygen–glucose deprivation and reoxygenation (OGD/RO) conditions. The in vivo experiment demonstrated that XBP improved the Neurologic Deficit Score (NDS), lowered the Neuron-Specific Enolase (NSE) level as well as reversed the typical neuropathological changes in PBI rats, indicating its neuroprotective effect on PBI. Further metabolomics analysis identified 94 differential metabolites after XBP treatment, and multiple metabolites were highly related to CIR. Moreover, network pharmacology results revealed that the therapeutic effect of XBP on PBI may be relevant to mitochondrial quality control (MQC). Mechanistically, XBP could not only promote the expressions of marker proteins including PGC1α, NRF1, TFAM, OPA1, MFN1 as well as MFN2 in mitochondrial biogenesis and mitochondrial fusion but also inhibit those proteins containing DRP1, MFF, FIS1, p62, PINK1, Parkin as well as LC3 in mitochondrial fission and mitophagy. Finally, AMP-activated protein kinase (AMPK) inhibitor was demonstrated to play a crucial role in regulating MQC.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533592","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}