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Modulation of Interhemispheric Synchronization and Cortical Activity in Healthy Subjects by High-Definition Theta-Burst Electrical Stimulation 高清晰度脉冲电刺激对健康受试者大脑半球同步和皮层活动的调节
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-29 DOI: 10.1155/2022/3593262
Van-Truong Nguyen, Chun-Wei Wu, Chien-An Chen, C. Lo, Fu-Yu Chen, Chun-I Wu, P. Sung, Chou-Ching K. Lin, Jia-Jin Chen
Background Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain. Methods In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively. Results The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06–0.15 Hz) and IV (0.02–0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions. Conclusions It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.
在重复经颅磁刺激(rTMS)过程中,各种形式的脉冲刺激(TBS)如间歇性TBS (iTBS)和连续TBS (cTBS)作为新的促进/抑制方案被引入,显示出比传统范式更好的效果。在此,我们将rTMS-TBS方案扩展到高清晰度蒙太奇(HD-TBS)电刺激,并研究其对人脑的神经效应。方法在受试者内设计中,15名右撇子健康成人随机参加10分钟和2 mA的HD-TBS会话:单侧(Uni)-iTBS,双侧(Bi)-cTBS/iTBS,以及对初级运动皮层区域的假刺激。在双侧前额叶皮层(PFC)、感觉运动皮层(SMC)和顶叶(PL)上覆盖20通道近红外光谱(NIRS)系统,观察静息状态和快速手指敲击任务在刺激前、刺激中和刺激后的脑血流动力学反应。研究了静息状态近红外光谱(NIRS)的半球间相关系数(IHCC)和小波相位相干性(WPCO),以及快速敲击手指时的血红蛋白浓度,分别反映了两半球和皮层活动之间的对称性。结果Bi-cTBS/iTBS下SMC区域NIRS数据的IHCC和WPCO在低频段III (0.06 ~ 0.15 Hz)和IV (0.02 ~ 0.06 Hz)值相对较小,表明在时间和频率上都存在明显的非同步。此外,快速手指敲击运动诱导的SMC激活在Uni-iTBS期间以及Bi-cTBS/iTBS期间和之后显著增加。结论10 min和2 mA双ctbs /iTBS在初级运动皮质区域的两个半球上有效地调节了健康受试者SMC的半球间同步和皮层激活。我们的研究表明,双侧HD-TBS入路是一种有效的无创脑刺激方案,可能成为一种新的治疗方法,用于诱导神经调节对缺血性卒中或创伤性脑损伤引起的各种神经系统疾病的作用。
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引用次数: 0
Topologic Reorganization of White Matter Connectivity Networks in Early-Blind Adolescents 早期失明青少年白质连接网络的拓扑重组
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-28 DOI: 10.1155/2022/8034757
Zhifeng Zhou, L. Qian, Jinping Xu, Yumin Lu, Fen Hou, Jingyi Zhou, Jinpei Luo, Gangqiang Hou, Wentao Jiang, Hengguo Li, Xia Liu
Blindness studies are important models for the comprehension of human brain development and reorganization, after visual deprivation early in life. To investigate the global and local topologic alterations and to identify specific reorganized neural patterns in early-blind adolescents (EBAs), we applied diffusion tensor tractography and graph theory to establish and analyze the white matter connectivity networks in 21 EBAs and 22 age- and sex-matched normal-sighted controls (NSCs). The network profiles were compared between the groups using a linear regression model, and the associations between clinical variables and network profiles were analyzed. Graph theory analysis revealed “small-world” attributes in the structural connection networks of both EBA and NSC cohorts. The EBA cohort exhibited significant lower network density and global and local efficiency, as well as significantly elevated shortest path length, compared to the NSC group. The network efficiencies were markedly reduced in the EBA cohort, with the largest alterations in the default-mode, visual, and limbic areas. Moreover, decreased regional efficiency and increased nodal path length in some visual and default-mode areas were strongly associated with the period of blindness in EBA cohort, suggesting that the function of these areas would gradually weaken in the early-blind brains. Additionally, the differences in hub distribution between the two groups were mainly within the occipital and frontal areas, suggesting that neural reorganization occurred in these brain regions after early visual deprivation during adolescence. This study revealed that the EBA brain structural network undergoes both convergent and divergent topologic reorganizations to circumvent early visual deprivation. Our research will add to the growing knowledge of underlying neural mechanisms that govern brain reorganization and development, under conditions of early visual deprivation.
失明研究是理解早期视觉剥夺后人类大脑发育和重组的重要模型。为了研究早期失明青少年(eba)的整体和局部拓扑改变,并识别特定的重组神经模式,我们应用扩散张量神经束成像和图论建立并分析了21名早期失明青少年和22名年龄和性别匹配的正常视力对照(NSCs)的白质连接网络。采用线性回归模型比较两组间的网络概况,并分析临床变量与网络概况之间的关系。图论分析揭示了EBA和NSC群体结构连接网络的“小世界”属性。与NSC组相比,EBA组的网络密度、整体和局部效率显著降低,最短路径长度显著增加。在EBA队列中,网络效率显著降低,默认模式、视觉和边缘区域的变化最大。此外,在EBA队列中,部分视觉和默认模式区域的效率下降和节点路径长度增加与失明时间密切相关,表明这些区域的功能在早期失明的大脑中逐渐减弱。此外,两组之间中枢分布的差异主要集中在枕叶和额叶区域,这表明在青春期早期视觉剥夺后,这些大脑区域发生了神经重组。本研究表明,EBA脑结构网络经历了收敛和发散的拓扑重组,以避免早期视觉剥夺。我们的研究将增加对早期视觉剥夺条件下控制大脑重组和发育的潜在神经机制的不断增长的知识。
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引用次数: 0
Short-Term Spinal Cord Stimulation or Pulsed Radiofrequency for Elderly Patients with Postherpetic Neuralgia: A Prospective Randomized Controlled Trial 短期脊髓刺激或脉冲射频治疗老年带状疱疹后神经痛:一项前瞻性随机对照试验
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-27 DOI: 10.1155/2022/7055697
Lei Sheng, Zihao Liu, Wang Zhou, Xiaojun Li, Xin Wang, Qingjuan Gong
Background Postherpetic neuralgia (PHN) is the most common and severe complication after varicella-zoster infection, especially in elderly patients. PHN is always refractory to treatment. Both pulsed radiofrequency (PRF) and short-term spinal cord stimulation (stSCS) have been used as effective analgesia methods in clinic. However, which technique could provide better pain relief remains unknown. Objectives This study is aimed at evaluating the efficacy and safety of PRF and stSCS in elderly patients with PHN. Study Design. A prospective, randomized-controlled study. Setting. Department of Pain Management, the Second Affiliated Hospital of Guangzhou Medical University. Methods A total of 70 elderly patients with PHN were equally randomized to the PRF group or stSCS group. Patients in the PRF group received PRF treatment, while patients in the stSCS group received stSCS treatment. The primary outcome was the effective rate. The secondary outcomes included the Visual Analogue Scale (VAS), the 36-Item Short Form Health Survey Questionnaire (SF-36), and the pregabalin dosage. All outcomes were evaluated at baseline and at different postoperative time points. Results At 12 months after surgery, the effective rate reached 79.3% in stSCS group, while 42.1% in PRF group. The effective rate was significantly higher in the stSCS group than in the PRF group at 3, 6, and 12 months after surgery. VAS scores decreased significantly at each postoperative time point in both groups (P < 0.001). The VAS scores were significantly lower in the stSCS group than in the PRF group at 3, 6, and 12 months after surgery. SF-36 scores (bodily pain and the physical role) were significantly improved at each postoperative time point in both groups (P < 0.001). The SF-36 scores were significantly higher in the stSCS group than in the PRF group at some postoperative time points. The pregabalin dosage was significantly lower in the stSCS group than in the PRF group at 3, 6, and 12 months after surgery. Limitations. A single-center study with a relatively small sample size. Conclusions Both PRF and stSCS are effective and safe neuromodulation techniques for elderly patients with PHN. However, stSCS could provide better and longer-lasting analgesic effect compared to PRF.
背景带状疱疹后疱疹性神经痛(PHN)是水痘-带状疱疹感染后最常见和最严重的并发症,尤其是在老年患者中。PHN总是难以治疗。脉冲射频(PRF)和短期脊髓刺激(stSCS)都是临床上有效的镇痛方法。然而,哪种技术可以更好地缓解疼痛仍然是未知的。目的评价PRF和stSCS治疗老年PHN患者的疗效和安全性。研究设计。一项前瞻性、随机对照研究。设置。广州医科大学第二附属医院疼痛管理科。方法将70例老年PHN患者随机分为PRF组和stSCS组。PRF组患者接受PRF治疗,stSCS组患者接受stSCS治疗。主要观察指标为有效率。次要结果包括视觉模拟量表(VAS)、36项简明健康调查问卷(SF-36)和普瑞巴林剂量。所有结果在基线和术后不同时间点进行评估。结果术后12个月,stSCS组有效率为79.3%,PRF组有效率为42.1%。术后3、6、12个月,stSCS组的有效率明显高于PRF组。两组术后各时间点VAS评分均显著降低(P < 0.001)。术后3、6、12个月,stSCS组的VAS评分明显低于PRF组。两组术后各时间点SF-36评分(躯体疼痛和躯体作用)均显著改善(P < 0.001)。术后部分时间点,stSCS组SF-36评分明显高于PRF组。术后3、6、12个月,stSCS组普瑞巴林剂量明显低于PRF组。的局限性。单中心研究,样本量相对较小。结论PRF和stSCS是治疗老年PHN患者有效、安全的神经调节技术。与PRF相比,stSCS能提供更好、更持久的镇痛效果。
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引用次数: 4
LANCL1 as the Key Immune Marker in Neuropathic Pain LANCL1作为神经性疼痛的关键免疫标志物
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-25 DOI: 10.1155/2022/9762244
Yu Shi, Xuefei Zhang, Q. Fang, Hongrui Zhan, Xianglong Wang, Xi-yan Huang, Tao Fan, Wei Liu, Wen-Tao Wu
Objective This study is to explore key immune markers and changes of immune microenvironment in neuropathic pain (NeuP). Method The data sets of GSE145199 and GSE145226 in Gene Expression Omnibus (GEO) database was used to analyze, and the key immune markers were verified by GSE70006 and GSE91396, and the infiltration degree of immune cells in different samples were analyzed by CIBERSORT analysis package. Results In this study, we found a key immune marker, namely, LANCL1. Regulatory axis closely related to LANCL1 has also been found, namely, miR-6325/LANCL1 axis. In the immune infiltration analysis, we also found that the LANCL1 is positively correlated with T cells CD4 naïve (r = 0.880, p < 0.05). Conclusion In this study, we found that LANCL1 may be a protective factor for NeuP, and the miR-6325/LANCL1 axis may be involved in the occurrence and development of NeuP. Cascade reactions including mast cells, macrophages, and T cells may be an important reason for the aggravation of nerve damage.
目的探讨神经性疼痛(NeuP)的关键免疫标志物及免疫微环境的变化。方法利用GEO数据库中GSE145199和GSE145226的数据集进行分析,通过GSE70006和GSE91396对关键免疫标记进行验证,并通过CIBERSORT分析包分析不同样品中免疫细胞的浸润程度。结果在本研究中,我们发现了一个关键的免疫标记,即LANCL1。还发现了与LANCL1密切相关的调控轴,即miR-6325/LANCL1轴。在免疫浸润分析中,我们还发现LANCL1与T细胞CD4 naïve呈正相关(r = 0.880, p < 0.05)。在本研究中,我们发现LANCL1可能是NeuP的保护因子,miR-6325/LANCL1轴可能参与了NeuP的发生发展。包括肥大细胞、巨噬细胞和T细胞在内的级联反应可能是神经损伤加重的重要原因。
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引用次数: 2
Revealing the Neuroimaging Mechanism of Acupuncture for Poststroke Aphasia: A Systematic Review 揭示针刺治疗脑卒中后失语的神经影像学机制:系统综述
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-21 DOI: 10.1155/2022/5635596
Boxuan Li, Shizhe Deng, Bo-lin Sang, Weiming Zhu, Bifang Zhuo, Menglong Zhang, Chenyang Qin, Yuanhao Lyu, Yuzheng Du, Zhihong Meng
Background Aphasia is a common symptom in stroke patients, presenting with the impairment of spontaneous speech, repetition, naming, auditory comprehension, reading, and writing function. Multiple rehabilitation methods have been suggested for the recovery of poststroke aphasia, including medication treatment, behavioral therapy, and stimulation approach. Acupuncture has been proven to have a beneficial effect on improving speech functions in repetition, oral speech, reading, comprehension, and writing ability. Neuroimaging technology provides a visualized way to explore cerebral neural activity, which helps reveal the therapeutic effect of acupuncture therapy. In this systematic review, we aim to reveal and summarize the neuroimaging mechanism of acupuncture therapy on poststroke aphasia to provide the foundation for further study. Methods Seven electronic databases were searched including PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang databases, and the Chinese Scientific Journal Database. After screening the studies according to the inclusion and exclusion criteria, we summarized the neuroimaging mechanism of acupuncture on poststroke aphasia, as well as the utilization of acupuncture therapy and the methodological characteristics. Result After searching, 885 articles were retrieved. After removing the literature studies, animal studies, and case reports, 16 studies were included in the final analysis. For the acupuncture type, 10 studies used manual acupuncture and 5 studies used electroacupuncture, while body acupuncture (10 studies), scalp acupuncture (7 studies), and tongue acupuncture (8 studies) were applied for poststroke aphasia patients. Based on blood oxygen level-dependent (BOLD) and diffusion tensor imaging (DTI) technologies, 4 neuroimaging analysis methods were used including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), seed-based analysis, and independent component analysis (ICA). Two studies reported the instant acupuncture effect, and 14 studies reported the constant acupuncture's effect on poststroke aphasia patients. 5 studies analyzed the correlation between the neuroimaging outcomes and the clinical language scales. Conclusion In this systematic review, we found that the mechanism of acupuncture's effect might be associated with the activation and functional connectivity of language-related brain areas, such as brain areas around Broca's area and Wernicke's area in the left inferior temporal gyrus, supramarginal gyrus, middle frontal gyrus, and inferior frontal gyrus. However, these studies were still in the preliminary stage. Multicenter randomized controlled trials (RCT) with large sample sizes were needed to verify current evidence, as well as to explore deeply the neuroimaging mechanisms of acupuncture's effects.
失语是脑卒中患者的常见症状,表现为自发言语、重复、命名、听觉理解、阅读和写作功能的损害。脑卒中后失语症的康复有多种方法,包括药物治疗、行为治疗和刺激治疗。针灸已被证明对提高重复、口语、阅读、理解和写作能力的语言功能有有益的影响。神经成像技术提供了一种可视化的方法来探索大脑神经活动,有助于揭示针灸治疗的治疗效果。本综述旨在揭示和总结针刺治疗脑卒中后失语的神经影像学机制,为进一步研究提供基础。方法检索PubMed、Web of Science、Embase、Cochrane中央对照试验库、中国国家知识基础设施、万方数据库、中国科学期刊数据库等7个电子数据库。根据纳入标准和排除标准对研究进行筛选后,总结针刺治疗脑卒中后失语的神经影像学机制、针刺治疗的应用及方法学特点。结果检索到文献885篇。在剔除文献研究、动物研究和病例报告后,16项研究被纳入最终分析。针刺类型采用手针10项,电针5项,体针(10项)、头皮针(7项)、舌针(8项)治疗脑卒中后失语症。基于血氧水平依赖(BOLD)和扩散张量成像(DTI)技术,采用低频波动幅度(ALFF)、区域均匀性(ReHo)、种子分析(seed-based analysis)和独立成分分析(ICA) 4种神经影像学分析方法。两项研究报告了即时针灸效果,14项研究报告了持续针灸对中风后失语症患者的影响。5项研究分析了神经影像学结果与临床语言量表的相关性。结论针刺的作用机制可能与左颞下回、边缘上回、额中回、额下回等与语言相关的脑区Broca’s区和Wernicke’s区周围的脑区激活和功能连接有关。然而,这些研究仍处于初步阶段。需要大样本量的多中心随机对照试验(RCT)来验证现有证据,并深入探讨针刺作用的神经影像学机制。
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引用次数: 4
Dexmedetomidine Mitigates Microglial Activation Associated with Postoperative Cognitive Dysfunction by Modulating the MicroRNA-103a-3p/VAMP1 Axis 右美托咪定通过调节MicroRNA-103a-3p/VAMP1轴减轻与术后认知功能障碍相关的小胶质细胞激活
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-19 DOI: 10.1155/2022/1353778
Zhichao Wu, Han Wang, Zuan Shi, Yalan Li
Surgery-induced microglial activation is critical in mediating postoperative cognitive dysfunction (POCD) in elderly patients, where the important protective effect of dexmedetomidine has been indicated. However, the mechanisms of action of dexmedetomidine during the neuroinflammatory response that underlies POCD remain largely unknown. We found that lipopolysaccharide (LPS) induced substantial inflammatory responses in primary and BV2 microglial cells. The screening of differentially expressed miRNAs revealed that miR-103a-3p was downregulated in these cell culture models. Overexpression of miR-103a-3p mimics and inhibitors suppressed and enhanced the release of inflammatory factors, respectively. VAMP1 expression was upregulated in LPS-treated primary and BV-2 microglial cells, and it was validated as a downstream target of miR-103-3p. VAMP1-knockdown significantly inhibited the LPS-induced inflammatory response. Dexmedetomidine treatment markedly inhibited LPS-induced inflammation and the expression of VAMP1, and miR-103a-3p expression reversed this inhibition. Moreover, dexmedetomidine mitigated microglial activation and the associated inflammatory response in a rat model of surgical trauma that mimicked POCD. In this model, dexmedetomidine reversed miR-103a-3p and VAMP1 expression; this effect was abolished by miR-103a-3p overexpression. Taken together, the data show that miR-103a-3p/VAMP1 is critical for surgery-induced microglial activation of POCD.
手术诱导的小胶质细胞激活是介导老年患者术后认知功能障碍(POCD)的关键,右美托咪定在这方面具有重要的保护作用。然而,右美托咪定在POCD背后的神经炎症反应中的作用机制在很大程度上仍然未知。我们发现脂多糖(LPS)在原代和BV2小胶质细胞中诱导了大量的炎症反应。筛选差异表达的mirna发现,miR-103a-3p在这些细胞培养模型中下调。过表达miR-103a-3p模拟物和抑制剂分别抑制和增强炎症因子的释放。VAMP1在lps处理的原代和BV-2小胶质细胞中表达上调,并被证实是miR-103-3p的下游靶点。vamp1敲低显著抑制lps诱导的炎症反应。右美托咪定治疗显著抑制lps诱导的炎症和VAMP1的表达,miR-103a-3p的表达逆转了这种抑制。此外,右美托咪定在模拟POCD的手术创伤大鼠模型中减轻了小胶质细胞的激活和相关的炎症反应。在该模型中,右美托咪定逆转了miR-103a-3p和VAMP1的表达;过表达miR-103a-3p可消除这种作用。综上所述,数据表明miR-103a-3p/VAMP1对于手术诱导的POCD小胶质细胞激活至关重要。
{"title":"Dexmedetomidine Mitigates Microglial Activation Associated with Postoperative Cognitive Dysfunction by Modulating the MicroRNA-103a-3p/VAMP1 Axis","authors":"Zhichao Wu, Han Wang, Zuan Shi, Yalan Li","doi":"10.1155/2022/1353778","DOIUrl":"https://doi.org/10.1155/2022/1353778","url":null,"abstract":"Surgery-induced microglial activation is critical in mediating postoperative cognitive dysfunction (POCD) in elderly patients, where the important protective effect of dexmedetomidine has been indicated. However, the mechanisms of action of dexmedetomidine during the neuroinflammatory response that underlies POCD remain largely unknown. We found that lipopolysaccharide (LPS) induced substantial inflammatory responses in primary and BV2 microglial cells. The screening of differentially expressed miRNAs revealed that miR-103a-3p was downregulated in these cell culture models. Overexpression of miR-103a-3p mimics and inhibitors suppressed and enhanced the release of inflammatory factors, respectively. VAMP1 expression was upregulated in LPS-treated primary and BV-2 microglial cells, and it was validated as a downstream target of miR-103-3p. VAMP1-knockdown significantly inhibited the LPS-induced inflammatory response. Dexmedetomidine treatment markedly inhibited LPS-induced inflammation and the expression of VAMP1, and miR-103a-3p expression reversed this inhibition. Moreover, dexmedetomidine mitigated microglial activation and the associated inflammatory response in a rat model of surgical trauma that mimicked POCD. In this model, dexmedetomidine reversed miR-103a-3p and VAMP1 expression; this effect was abolished by miR-103a-3p overexpression. Taken together, the data show that miR-103a-3p/VAMP1 is critical for surgery-induced microglial activation of POCD.","PeriodicalId":19122,"journal":{"name":"Neural Plasticity","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74526165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice 生长激素增加小鼠光血栓性中风后特定脑区BDNF和mTOR的表达
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-15 DOI: 10.1155/2022/9983042
Sonia Sanchez-Bezanilla, Daniel J. Beard, R. Hood, N. Åberg, P. Crock, F. Walker, M. Nilsson, J. Isgaard, L. Ong
Aims We have shown that growth hormone (GH) treatment poststroke increases neuroplasticity in peri-infarct areas and the hippocampus, improving motor and cognitive outcomes. We aimed to explore the mechanisms of GH treatment by investigating how GH modulates pathways known to induce neuroplasticity, focusing on association between brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the peri-infarct area, hippocampus, and thalamus. Methods Recombinant human growth hormone (r-hGH) or saline was delivered (0.25 μl/hr, 0.04 mg/day) to mice for 28 days, commencing 48 hours after photothrombotic stroke. Protein levels of pro-BDNF, total-mTOR, phosphorylated-mTOR, total-p70S6K, and phosporylated-p70S6K within the peri-infarct area, hippocampus, and thalamus were evaluated by western blotting at 30 days poststroke. Results r-hGH treatment significantly increased pro-BDNF in peri-infarct area, hippocampus, and thalamus (p < 0.01). r-hGH treatment significantly increased expression levels of total-mTOR in the peri-infarct area and thalamus (p < 0.05). r-hGH treatment significantly increased expression of total-p70S6K in the hippocampus (p < 0.05). Conclusion r-hGH increases pro-BDNF within the peri-infarct area and regions that are known to experience secondary neurodegeneration after stroke. Upregulation of total-mTOR protein expression in the peri-infarct and thalamus suggests that this might be a pathway that is involved in the neurorestorative effects previously reported in these animals and warrants further investigation. These findings suggest region-specific mechanisms of action of GH treatment and provide further understanding for how GH treatment promotes neurorestorative effects after stroke.
我们已经证明,脑卒中后生长激素(GH)治疗增加了梗死周围区域和海马的神经可塑性,改善了运动和认知结果。我们的目的是通过研究生长激素如何调节已知的诱导神经可塑性的途径来探索生长激素的治疗机制,重点研究脑源性神经营养因子(BDNF)和哺乳动物雷帕霉素靶蛋白(mTOR)在梗死周围区、海马和丘脑中的关联。方法在光血栓性脑卒中后48 h,给药小鼠重组人生长激素(r-hGH)或生理盐水(0.25 μl/hr, 0.04 mg/day) 28 d。脑卒中后30天,采用western blotting检测梗死周围区、海马和丘脑中pro-BDNF、总mtor、磷酸化mtor、总p70s6k和磷酸化p70s6k的蛋白水平。结果r-hGH显著提高了梗死周围区、海马和丘脑中bdnf的表达(p < 0.01)。r-hGH显著提高梗死周围区和丘脑总mtor表达水平(p < 0.05)。r-hGH处理显著增加海马总p70s6k的表达(p < 0.05)。结论r-hGH增加脑卒中后梗死周围区域和已知发生继发性神经退行性变的区域的bdnf。梗死周围和丘脑中总mtor蛋白表达的上调表明,这可能是一种参与先前在这些动物中报道的神经恢复作用的途径,值得进一步研究。这些发现提示了生长激素治疗的区域特异性作用机制,并为生长激素治疗如何促进脑卒中后神经恢复作用提供了进一步的理解。
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引用次数: 1
Cognitive Dysfunction following Cerebellar Stroke: Insights Gained from Neuropsychological and Neuroimaging Research 脑卒中后的认知功能障碍:从神经心理学和神经影像学研究中获得的见解
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-15 DOI: 10.1155/2022/3148739
Qi Liu, Chang-bin Liu, Yu Chen, Yumei Zhang
Although the cerebellum has been consistently noted in the process of cognition, the pathophysiology of this link is still under exploration. Cerebellar stroke, in which the lesions are focal and limited, provides an appropriate clinical model disease for studying the role of the cerebellum in the cognitive process. This review article targeting the cerebellar stroke population (1) describes a cognitive impairment profile, (2) identifies the cerebellar structural alterations linked to cognition, and (3) reveals possible mechanisms of cerebellar cognition using functional neuroimaging. The data indicates the disruption of the cerebro-cerebellar loop in cerebellar stroke and its contribution to cognitive dysfunctions. And the characteristic of cognitive deficits are mild, span a broad spectrum, dominated by executive impairment. The consideration of these findings could contribute to deeper and more sophisticated insights into the cognitive function of the cerebellum and might provide a novel approach to cognitive rehabilitation. The goal of this review is to spread awareness of cognitive impairments in cerebellar disorders.
虽然小脑在认知过程中一直被注意到,但这种联系的病理生理学仍在探索中。小脑卒中的病变是局灶性和局限性的,为研究小脑在认知过程中的作用提供了一种合适的临床模型疾病。这篇针对小脑卒中人群的综述文章(1)描述了认知障碍概况,(2)确定了与认知相关的小脑结构改变,(3)利用功能性神经影像学揭示了小脑认知的可能机制。数据表明小脑卒中中脑-小脑回路的破坏及其对认知功能障碍的贡献。认知缺陷的特征是轻微的,范围广泛,以执行能力障碍为主。对这些发现的考虑可能有助于对小脑的认知功能有更深入和更复杂的了解,并可能为认知康复提供一种新的方法。这篇综述的目的是传播认知障碍在小脑疾病的认识。
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引用次数: 4
Enriched Environment Effects on Myelination of the Central Nervous System: Role of Glial Cells 富集环境对中枢神经系统髓鞘形成的影响:胶质细胞的作用
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-14 DOI: 10.1155/2022/5766993
Zhen-Kun Gao, Xin-Ya Shen, Yu Han, Yi-Sha Guo, Mei Yuan, Xia Bi
Myelination is regulated by various glial cells in the central nervous system (CNS), including oligodendrocytes (OLs), microglia, and astrocytes. Myelination of the CNS requires the generation of functionally mature OLs from OPCs. OLs are the myelin-forming cells in the CNS. Microglia play both beneficial and detrimental roles during myelin damage and repair. Astrocyte is responsible for myelin formation and regeneration by direct interaction with oligodendrocyte lineage cells. These glial cells are influenced by experience-dependent activities such as environmental enrichment (EE). To date, there are few studies that have investigated the association between EE and glial cells. EE with a complex combination of sensorimotor, cognitive, and social stimulation has a significant effect on cognitive impairment and brain plasticity. Hence, one mechanism through EE improving cognitive function may rely on the mutual effect of EE and glial cells. The purpose of this paper is to review recent research into the efficacy of EE for myelination and glial cells at cellular and molecular levels and offers critical insights for future research directions of EE and the treatment of EE in cognitive impairment disease.
髓鞘形成受中枢神经系统(CNS)中多种胶质细胞的调控,包括少突胶质细胞(OLs)、小胶质细胞和星形胶质细胞。中枢神经系统的髓鞘形成需要OPCs生成功能成熟的ol。ol是中枢神经系统中的髓磷脂形成细胞。小胶质细胞在髓磷脂损伤和修复过程中起着有益和有害的作用。星形胶质细胞通过与少突胶质细胞系细胞的直接相互作用,负责髓磷脂的形成和再生。这些神经胶质细胞受到经验依赖活动的影响,如环境富集(EE)。迄今为止,很少有研究调查情感表达与神经胶质细胞之间的关系。情感表达与感觉运动、认知和社会刺激的复杂组合对认知障碍和大脑可塑性有显著影响。因此,情感表达改善认知功能的一种机制可能依赖于情感表达和神经胶质细胞的相互作用。本文旨在从细胞和分子水平综述近期关于情感表达对髓鞘细胞和胶质细胞的作用的研究,并为情感表达未来的研究方向以及情感表达在认知障碍疾病中的治疗提供重要见解。
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引用次数: 3
Identifying Key Biomarkers and Immune Infiltration in Female Patients with Ischemic Stroke Based on Weighted Gene Co-Expression Network Analysis 基于加权基因共表达网络分析的女性缺血性卒中患者关键生物标志物和免疫浸润识别
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-04-08 DOI: 10.1155/2022/5379876
Haipeng Xu, Kelin He, Rong Hu, Yanzhi Ge, Xinyun Li, F. Ni, Bei Que, Yi Chen, Ruijie Ma
Stroke is one of the leading causes of death and disability worldwide. Evidence shows that ischemic stroke (IS) accounts for nearly 80 percent of all strokes and that the etiology, risk factors, and prognosis of this disease differ by gender. Female patients may bear a greater burden than male patients. The immune system may play an important role in the pathophysiology of females with IS. Therefore, it is critical to investigate the key biomarkers and immune infiltration of female IS patients to develop effective treatment methods. Herein, we used weighted gene co-expression network analysis (WGCNA) to determine the key modules and core genes in female IS patients using the GSE22255, GSE37587, and GSE16561 datasets from the GEO database. Subsequently, we performed functional enrichment analysis and built a protein-protein interaction (PPI) network. Ten genes were selected as the true central genes for further investigation. After that, we explored the specific molecular and biological functions of these hub genes to gain a better understanding of the underlying pathogenesis of female IS patients. Moreover, the “Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT)” was used to examine the distribution pattern of immune subtypes in female patients with IS and normal controls, revealing a new potential target for clinical treatment of the disease.
中风是全世界导致死亡和残疾的主要原因之一。有证据表明,缺血性中风(IS)占所有中风的近80%,其病因、危险因素和预后因性别而异。女性患者可能比男性患者承受更大的负担。免疫系统可能在IS女性的病理生理中发挥重要作用。因此,研究女性is患者的关键生物标志物和免疫浸润对制定有效的治疗方法至关重要。本文采用加权基因共表达网络分析(WGCNA),利用GEO数据库中的GSE22255、GSE37587和GSE16561数据集,确定女性IS患者的关键模块和核心基因。随后,我们进行了功能富集分析,并建立了蛋白质-蛋白质相互作用(PPI)网络。选出10个基因作为真正的中心基因进行进一步研究。之后,我们探索了这些枢纽基因的特定分子和生物学功能,以更好地了解女性IS患者的潜在发病机制。此外,利用“Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT)”检测女性IS患者和正常对照中免疫亚型的分布模式,揭示了临床治疗该疾病的新的潜在靶点。
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引用次数: 2
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Neural Plasticity
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