CNS Neuroscience & Therapeutics最新文献

{"title":"Correction to “Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism”","authors":"","doi":"10.1111/cns.70387","DOIUrl":"https://doi.org/10.1111/cns.70387","url":null,"abstract":"<p>Y. Y. Bai, X. G. Peng, L. S. Wang, Z. H. Li, Y. C. Wang, C. Q. Lu, J. Ding, P. C. Li, Z. Zhao, and S. H. Ju, “Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism,” <i>CNS Neuroscience &amp; Therapeutics</i> 21, no. 11 (2015): 877–886. https://doi.org/10.1111/cns.12447.</p><p>In the original version of our article, there was an error in Figure 3A. Specifically, the immunohistochemical image of NeuN for the MCAO group was incorrect. The correct image is provided below. This correction will not affect the results and conclusion.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801314","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":"TRPC4 Mediates Trigeminal Neuropathic Pain via Ca2+-ERK/P38-ATF2 Pathway in the Trigeminal Ganglion of Mice","authors":"Xinlong Ke,&nbsp;Huajing Cai,&nbsp;Fangla Luo,&nbsp;Xing Zheng,&nbsp;Qian Hu,&nbsp;Youfa Zhou,&nbsp;Yongjie Wang,&nbsp;Xiangnan Zhang,&nbsp;Yeru Chen,&nbsp;Gang Chen","doi":"10.1111/cns.70368","DOIUrl":"https://doi.org/10.1111/cns.70368","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;Trigeminal neuropathic pain (TNP) is a debilitating condition characterized by chronic facial pain, yet its underlying mechanisms remain incompletely understood. Transient Receptor Potential Canonical 4 (TRPC4) has been reported to promote the development of abnormal pain or pain hypersensitivity in neuropathic pain. However, the specific contribution of TRPC4 to TNP pathogenesis remains unclear.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to investigate the role of TRPC4 in a mouse model of trigeminal neuropathic pain induced by chronic constriction of the unilateral infraorbital nerve (CION).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Adult male/female mice were subjected to either CION surgery or sham surgery. Behavioral assays were conducted to assess facial pain-like responses over a 28-day period. TRPC4 distribution in the trigeminal ganglion (TG) was evaluated using Immunofluorescence. TRPC4 inhibitor ML204 and agonist Englerin A were employed to evaluate the impact of TRPC4 on facial pain-like behaviors. A TRPC4-overexpressing HEK293 cell model was conducted via plasmid transfection. To assess the function of TRPC4, we employed cellular calcium imaging technology to investigate the effects of modulating TRPC4 function by analyzing dynamic changes in intracellular calcium ion concentrations in primary trigeminal ganglion neurons and HEK293 cells. &lt;i&gt;Trpc4&lt;/i&gt; shRNA was used to specifically knock down TRPC4 in the trigeminal ganglion. Western blot analysis was used to assess the activation of ERK, P38, and ATF2 signaling pathways.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Mice subjected to CION exhibited persistent facial pain-like behaviors and a significant increase in TRPC4 expression in TG neurons. &lt;i&gt;Trpc4&lt;/i&gt; shRNA or pharmacological inhibition with ML204 attenuated CION-induced pain behaviors, while activation of TRPC4 with Englerin A induced pain-like responses in naive mice. Calcium imaging revealed that both Englerin A and TRPC4 overexpression elevated intracellular Ca²&lt;sup&gt;2+&lt;/sup&gt; levels in TG neurons and HEK293 cells. This Ca²&lt;sup&gt;2+&lt;/sup&gt; influx triggered the activation of ERK and P38, leading to enhanced ATF2 activation. Downregulation of TRPC4 in the TG reduced ERK/P38 phosphorylation and ATF2 expression and activation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study provides the first evidence that TRPC4 plays a critical role in CION-induced trigeminal ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801332","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":"Ultrasound-Induced Synchronized Neural Activities at 40 Hz and 200 Hz Entrained Corresponded Oscillations and Improve Alzheimer's Disease Memory","authors":"Jiamin Chen,&nbsp;Xingran Wang,&nbsp;Xin Li,&nbsp;Xiaoli Li,&nbsp;Yiyao Zhang,&nbsp;Yi Yuan","doi":"10.1111/cns.70351","DOIUrl":"https://doi.org/10.1111/cns.70351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Neurological diseases like Alzheimer's disease (AD) with cognitive deficits show impaired theta, gamma, and ripple bands. Restoring these oscillations may be crucial for rescuing cognitive functions. Low-intensity transcranial ultrasound stimulation (TUS), a noninvasive neuromodulation method, offers high spatial resolution and deep penetration. However, it remains unclear how 40 Hz and 200 Hz TUS may improve memory in AD by regulating hippocampal oscillations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We applied 40 Hz and 200 Hz TUS to the CA1 region of AD mice, performing memory assessments and CA1 electrophysiology recordings simultaneously.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that both 40 Hz and 200 Hz TUS significantly improved memory performance in AD mice by targeting the dorsal hippocampus and increasing power in corresponding frequency bands. Specifically, 40 Hz TUS enhanced gamma and ripple bands, while 200 Hz TUS strongly affected both. This enhancement increased during stimulation and persisted 5 days poststimulation. Improved coupling between theta and gamma oscillations indicated better hippocampal coordination with other brain regions. Additionally, 40 Hz TUS raised sharp wave ripple (SPW-Rs) incidence, and 200 Hz TUS increased both SPW-R incidence and duration, contributing to memory improvement. Behavioral performance significantly improved with TUS at both frequencies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ultrasound-induced synchronized neural activities at 40 Hz and 200 Hz entrained corresponding oscillations and improved memory in Alzheimer's disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801875","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":"Characterization of the Molecular Mechanisms Underlying Lurasidone-Induced Acute Manic Episodes in Bipolar Depression: A Network Pharmacology and Molecular Docking Approach","authors":"Chao Li,&nbsp;Lei Yang,&nbsp;Qiuyu Zhang,&nbsp;Ying Zhang,&nbsp;Ranli Li,&nbsp;Feng Jia,&nbsp;Lina Wang,&nbsp;Xiaoyan Ma,&nbsp;Hongjun Tian,&nbsp;Chuanjun Zhuo","doi":"10.1111/cns.70383","DOIUrl":"https://doi.org/10.1111/cns.70383","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lurasidone monotherapy has been approved for the treatment of bipolar depression. However, several case reports have indicated treatment with lurasidone-induced acute mania in people with bipolar depression. The mechanism by which this occurs remains to be elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this study, we systematically explored the mechanism of action of lurasidone-induced acute mania in bipolar depression using network pharmacology and molecular docking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Putative target genes for lurasidone were obtained from the GeneCards, PharmMapper, SwissTargetPrediction, and DrugBank databases. Targets for bipolar depression and acute mania were collected from the DisGeNET and GeneCards databases. A protein–protein interaction (PPI) network was built to screen the hub targets. The Bioinformatics platform and Database for Annotation, Visualization, and Integrated Discovery were used for the visualization of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the top 20 core targets. The drug-pathway-target-disease network was constructed using Cytoscape. Finally, molecular docking was performed to evaluate the binding affinity between lurasidone and potential targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 327, 1253, and 429 targets of lurasidone, bipolar depression, and acute mania were identified, respectively. A topological analysis of the PPI network revealed the top 20 hub targets. Based on PPI, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the top 20 hub targets, lurasidone was found to induce acute manic episodes in people with bipolar depression by targeting the serotonergic synapse signaling pathway via MAOB, HTR1A, HTR2A, HTR3A, SLC18A2, HTR1B, and HTR7. Molecular docking revealed good binding affinities between lurasidone and these potential targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study revealed that lurasidone may regulate the serotonergic synapse signaling pathway by interacting with the identified core targets MAOB, HTR1A, HTR2A, HTR3A, SLC18A2, HTR1B, and HTR7 to induce treatment-emergent mania in people with bipolar depression. Our work provides a theoretical basis for the pharmacology of lurasidone-induced acute mania in bipolar depression and further basic research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801320","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":"Optimized Mouse Model of Sepsis-Associated Encephalopathy: A Rational Standard Based on Modified SHIRPA Score and Neurobehaviors in Mice","authors":"Yuewen Xin,&nbsp;Mi Tian,&nbsp;Xu Pei,&nbsp;Shuixiang Deng,&nbsp;Yao Wang,&nbsp;Feng Zhao,&nbsp;Thomas Behnisch,&nbsp;Yanqin Gao,&nbsp;Ye Gong","doi":"10.1111/cns.70365","DOIUrl":"https://doi.org/10.1111/cns.70365","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis-associated encephalopathy (SAE), a severe neurological disorder, is marked by widespread brain dysfunction. At present, there is no universally accepted criterion for diagnosing SAE in animal models. This study proposes a standardized evaluation method for SAE in mice, addressing inconsistencies in current research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Using a cecal ligation and puncture (CLP) model to induce sepsis, we assessed the physiological status of mice with a modified SHIRPA score to differentiate SAE from non-SAE, validating our findings through various behavioral tests and evaluations of neuroinflammation and neuronal damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that the conventional mild–moderate–severe categorization of SHIRPA was insufficient for distinguishing between SAE and non-SAE. To enhance differentiation, we classified mice based on the median modified SHIRPA score, validating this approach through behavioral tests including the Y-maze, three-chamber social test, and open field test. This method effectively identified neurological impairments in septic mice. Further validation involved assessing neuronal damage, neuroinflammation, the Morris water maze, and long-term potentiation (LTP) in the hippocampal CA1 region. Results indicated that mice in the up-Median group exhibited greater neuroinflammation, neuronal injury, and cognitive deficits compared to the down-Median group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study establishes a reliable evaluation method for SAE in murine models, facilitating improved differentiation between SAE and non-SAE. Such advancements will enhance our understanding of the pathogenesis of SAE and guide more effective treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801401","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":"MeCP2 Modulates Depression-Like Behaviors Comorbid to Chronic Pain by Regulating Adult Hippocampal Neurogenesis","authors":"Yanting Sun,&nbsp;Ying Zhang,&nbsp;Yexiang Chen,&nbsp;Huisheng Peng,&nbsp;Tiantian Cheng,&nbsp;Xiujian Sun,&nbsp;Jing-Gen Liu,&nbsp;Chi Xu","doi":"10.1111/cns.70311","DOIUrl":"https://doi.org/10.1111/cns.70311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Although previous studies have revealed the association between chronic pain-induced depression and defective adult hippocampal neurogenesis (AHN), the underlying molecular mechanism remains elusive. This study aims to examine the association between AHN and depression-like behaviors, and to reveal the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The chronic neuropathic pain model was established using mice with the spared nerve injury (SNI) surgery. The depression-like behaviors were evaluated by using the sucrose preference test (SPT), the tail suspension test (TST), the forced swimming test (FST), and the open field test (OFT). The expression of Methyl-CpG-binding protein 2 (MeCP2) was modulated by injecting the adeno-associated virus (AAV) with the DIO system into the ventral DG of the <i>Nes</i>-CreER^T2 mice. The miRNAs in hippocampal neural stem cells (NSCs) of mice with chronic pain were analyzed via miRNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that MeCP2, an epigenetic factor that plays a key role in the development of neurons, was significantly down-regulated in NSCs in the dentate gyrus (DG) of the hippocampus in adult mice with chronic pain and comorbid depression, suggesting a role of MeCP2 in the regulation of depression-like behavior induced by chronic neuropathic pain. MeCP2 expression levels in hippocampal NSCs were closely related to AHN and chronic pain comorbid depression, and miR-199b-3p specifically targeted and inhibited MeCP2 expression by directly interacting with its 3’-UTR sequence. Furthermore, we demonstrated that the increased level of miR-199b-3p in NSCs after the occurrence of chronic pain was responsible for AHN inhibition and comorbid depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Chronic neuropathic pain may result in an increased level of miR-199b-3p in hippocampal NSCs, which in turn targeted the <i>Mecp2</i> gene and inhibited its transcription. Inhibited MeCP2 expression in NSCs contributes to AHN inhibition and depression-like behaviors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787256","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":"Additional Cover","authors":"","doi":"10.1111/cns.70388","DOIUrl":"https://doi.org/10.1111/cns.70388","url":null,"abstract":"<p>Cover image: The cover image is based on the article <i>Electroacupuncture Regulates Sympathetic Nerve Through the\u0000NTSGlu–RVLM Circuit to Relieve Spontaneous Pain in SNI Rats</i> by Wen Chen et al., https://doi.org/10.1111/cns.70327.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787049","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":"Hydrogen Sulfide Sustained Release Donor Alleviates Spinal Cord Ischemia–Reperfusion-Induced Neuron Death by Inhibiting Ferritinophagy-Mediated Ferroptosis","authors":"Lei Xie,&nbsp;Qiuping He,&nbsp;Hang Wu,&nbsp;Weipeng Shi,&nbsp;Xiao Xiao,&nbsp;Tengbo Yu","doi":"10.1111/cns.70366","DOIUrl":"https://doi.org/10.1111/cns.70366","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Spinal cord ischemia–reperfusion injury (SCIRI) is a disastrous complication that cannot be completely prevented in thoracoabdominal aneurysm surgery, leading to sensory and motor dysfunction and even paraparesis, causing tremendous socioeconomic burden. Ferritinophagy is a form of autophagic ferroptosis, which is a contributor to SCIRI. Hydrogen sulfide (H₂S) has been reported to be neuroprotective in various diseases. However, it remains unclear whether H₂S alleviates SCIRI-induced neural death via regulating ferritinophagy-mediated ferroptosis. The aim of this study was to explore their relationship and interaction in SCIRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results demonstrate that Nissl bodies and motor function were obviously lost in SCIRI rats. Meanwhile, SCIRI led to a significant increase in DHE-positive neurons, TUNEL-positive neurons, LC3-positive neurons, and ferritin-positive neurons, downregulation of GPx4, Slc7a11, p62, and ferritin expression, and upregulation of LC3 II/I and NCOA4 expression. Additionally, there was upregulation of the level of MDA, GSH, and Fe²⁺. Finally, we found that H₂S could significantly relieve neuronal death and loss of motor function in SCIRI rats by inhibiting ferritinophagy and ferroptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ferroptosis and ferritinophagy play a crucial role in the etiopathogenesis of SCIRI, and H₂S exerts neuroprotection by inhibiting ferritinophagy-mediated ferroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749741","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":"GAD65 Antibody-Associated Neurologic Syndrome Overlapping Hemophagocytic Lymphohistiocytosis","authors":"Ya Chen,&nbsp;Doujia Chen,&nbsp;Zhongxiang Xu,&nbsp;Zucai Xu","doi":"10.1111/cns.70364","DOIUrl":"https://doi.org/10.1111/cns.70364","url":null,"abstract":"&lt;p&gt;Glutamic acid decarboxylase 65 (GAD65) antibody-associated neurologic syndrome is a rare neurologic syndrome mediated by autoimmune response injury including autoimmune epilepsy, autoimmune cerebellar ataxia, stiff-person syndrome, and limbic encephalitis [&lt;span&gt;1&lt;/span&gt;]. Hemophagocytic lymphohistiocytosis (HLH) is a systemic inflammatory disease that can present with a variety of clinical manifestations [&lt;span&gt;2&lt;/span&gt;]. Both are associated with immunoinflammation, but no coexistence has been reported. Here, we report the first case of GAD65 antibody-associated neurologic syndrome overlap hemophagocytic lymphohistiocytosis.&lt;/p&gt;&lt;p&gt;A previously healthy 49-year-old man had a first generalized tonic-clonic seizure in May 2022. Two months after the initial presentation, he presented symptoms associated with cerebellar dysfunction, including dizziness, unstable walking. In September, he had another seizure with electroencephalogram showing low-to-medium amplitude sharp waves scattered in the focal left hemisphere and was treated with sodium valproate sustained-release tablets 500 mg twice daily. He presented with progressive dizziness and instability. In January 2023, he showed left tinnitus, deafness, diplopia, and was admitted to our hospital.&lt;/p&gt;&lt;p&gt;The neurologic examination revealed slight bradylalia, horizontal gaze nystagmus, diplopia but no limitation of eye movement, diminished tingling on the left side of the face, and an unstable heel-to-shin test. Brain magnetic resonance imaging (MRI) showed multiple abnormal signals without contrast enhancement lesions (Figure 1A). Electroencephalogram showed normal. An extensive screening for rheumatological disorders showed negative results, as did screening tests for metabolic, tumor, and infectious causes. Cerebrospinal fluid (CSF) examination revealed normal open pressure, 10 × 10&lt;sup&gt;6&lt;/sup&gt;/L leukocytes, 597 mg/L total protein, no heteromorphic cells, and normal glucose and chloride levels. There were CSF-specific oligoclonal bands (type II). Mitochondrial genetic testing, broad CSF microbiological examination, and CSF metagenomic next-generation sequencing were unremarkable. Other autoimmune encephalitis and paraneoplastic antibodies remained negative except positive anti-GAD65 antibodies detected by cell-based immunoassays in serum (1:30) and in CSF (1:10). After excluding other diseases, he was diagnosed with GAD65 antibody-associated neurologic syndrome. Meanwhile, hidden-malignancy screenings for chest, abdomen computed tomography, thyroid, superficial lymph nodes and breast ultrasound, gastroscopy, and colonoscopy were negative. He was prescribed intravenous methylprednisolone pulse therapy (1 g/day) for 5 days and gradually reduced the dosage to oral tapering prednisone, which alleviated his symptoms, especially diplopia and dizziness. The patient had been seizure-free since taking valproate.&lt;/p&gt;&lt;p&gt;After being discharged for 30 days, the patient became very weak and was readmitted for ab","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717127","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":"Cognitive Sequelae of COVID-19: Mechanistic Insights and Therapeutic Approaches","authors":"Yu-Hao Chen,&nbsp;Jing-Shiun Jan,&nbsp;Chih-Hao Yang,&nbsp;Ting-Lin Yen,&nbsp;Tran Thanh Duy Linh,&nbsp;Saileela Annavajjula,&nbsp;Mantosh Kumar Satapathy,&nbsp;Shin-Yi Tsao,&nbsp;Cheng-Ying Hsieh","doi":"10.1111/cns.70348","DOIUrl":"https://doi.org/10.1111/cns.70348","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The COVID-19 pandemic has left an indelible mark on the world, with mounting evidence suggesting that it not only posed acute challenges to global healthcare systems but has also unveiled a complex array of long-term consequences, particularly cognitive impairment (CI). As the persistence of post-COVID-19 neurological syndrome could evolve into the next public health crisis, it is imperative to gain a better understanding of the intricate pathophysiology of CI in COVID-19 patients and viable treatment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This comprehensive review explores the pathophysiology and management of cognitive impairment across the phases of COVID-19, from acute infection to Long-COVID, by synthesizing findings from clinical, preclinical, and mechanistic studies to identify key contributors to CI, as well as current therapeutic approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Key mechanisms contributing to CI include persistent neuroinflammation, cerebrovascular complications, direct neuronal injury, activation of the kynurenine pathway, and psychological distress. Both pharmacological interventions, such as anti-inflammatory therapies and agents targeting neuroinflammatory pathways, and non-pharmacological strategies, including cognitive rehabilitation, show promise in addressing these challenges. Although much of the current evidence is derived from preclinical and animal studies, these findings provide foundational insights into potential treatment approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By synthesizing current knowledge, this review highlights the importance of addressing COVID-19-related cognitive impairment and offers actionable insights for mitigation and recovery as the global community continues to grapple with the pandemic's long-term impact.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717193","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}