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p38 MAPK Endogenous Inhibition Improves Neurological Deficits in Global Cerebral Ischemia/Reperfusion Mice. p38 MAPK内源性抑制改善全脑缺血/再灌注小鼠的神经功能缺损。
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-06-29 eCollection Date: 2022-01-01 DOI: 10.1155/2022/3300327
Kun Hou, Zhi-Cheng Xiao, Hai-Long Dai

Cerebral ischemia/reperfusion (I/R) injury is a complex pathophysiological process that can lead to neurological function damage and the formation of cerebral infarction. The p38 MAPK pathway has attracted considerable attention in cerebral I/R injury (IRI), but little research has been carried out on its direct role in vivo. In this study, to observe the effects of p38 MAPK endogenous inhibition on cerebral IRI, p38 heterozygous knockdown (p38KI/+) mice were used. We hypothesized that p38 signaling might be involved in I/R injury and neurological damage reduction and that neurological behavioral deficits improve when p38 MAPK is inhibited. First, we examined the neurological damage and neurological behavioral deficit effects of I/R injury in WT mice. Cerebral I/R injury was induced by the bilateral common carotid artery occlusion (BCCAO) method. The cerebral infarction area and volume were assessed and analyzed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. p38 MAPK and caspase-3 were detected by western blotting. Neuronal apoptosis was measured using TUNEL staining. Neurological deficits were detected by behavioral testing. Furthermore, to assess whether these neuroprotective effects occurred when p38 MAPK was inhibited, p38 heterozygous knockdown (p38KI/+) mice were used. We found that p38 MAPK endogenous inhibition rescued hippocampal cell apoptosis, reduced ischemic penumbra, and improved neurological behavioral deficits. These findings showed that p38 MAPK endogenous inhibition had a neuroprotective effect on IRI and that p38 MAPK may be a potential therapeutic target for cerebral IRI.

脑缺血再灌注损伤是一个复杂的病理生理过程,可导致神经功能损伤和脑梗死的形成。p38 MAPK通路在脑I/R损伤(IRI)中引起了广泛的关注,但关于其在体内的直接作用的研究很少。本研究以p38杂合敲低(p38KI/+)小鼠为实验对象,观察p38 MAPK内源性抑制对脑IRI的影响。我们假设p38信号可能参与I/R损伤和神经损伤减轻,当p38 MAPK被抑制时,神经行为缺陷得到改善。首先,我们研究了I/R损伤对WT小鼠的神经损伤和神经行为缺陷的影响。采用双侧颈总动脉闭塞法(BCCAO)诱导脑I/R损伤。采用2,3,5-三苯基四唑氯(TTC)染色法评估脑梗死面积和脑梗死体积。western blotting检测p38 MAPK和caspase-3。TUNEL染色检测神经元凋亡。通过行为测试检测神经功能缺损。此外,为了评估当p38 MAPK被抑制时是否会发生这些神经保护作用,我们使用了p38杂合敲低(p38KI/+)小鼠。我们发现p38 MAPK内源性抑制挽救了海马细胞凋亡,减少了缺血半暗区,改善了神经行为缺陷。这些发现表明p38 MAPK内源性抑制对IRI具有神经保护作用,p38 MAPK可能是脑IRI的潜在治疗靶点。
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引用次数: 3
Quantitative and Fiber-Selective Evaluation for Central Poststroke Pain 中枢性脑卒中后疼痛的定量和纤维选择性评估
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-06-06 DOI: 10.1155/2022/1507291
Jian-Min Chen, Qing-Fa Chen, Zhi-Yong Wang, Guo-Xin Ni
The electrophysiological recording can be used to quantify the clinical features of central poststroke pain (CPSP) caused by different lesion locations. We aimed to explore the relationship between clinical features and lesion location in patients with CPSP using the current perception threshold (CPT) approach. Here, patients underwent the standardized CPT measure at five detection sites on both the contralesional and ipsilesional sides, using a constant alternating-current sinusoid waveform stimulus at three frequencies: 2000 Hz, 250 Hz, and 5 Hz. 57 CPSP patients were recruited in this cross-sectional study, including 13 patients with thalamic lesions and 44 patients with internal capsule lesions. Patients with a thalamic lesion had more frequent abnormal Aδ and C fibers than those with an internal capsule lesion (69.2% versus 36.4%, p value = 0.038; 53.8% versus 63.6%, p value = 0.038). The patients with internal capsule lesions had more frequent abnormal Aβ fibers than those with thalamic lesions (53.8% versus 63.6%, p value < 0.001). The sensory dysfunction in the patients with thalamic lesions was more likely to occur in the upper limbs (i.e., the shoulder (p value = 0.027) and the finger (p value = 0.040)). The lower limbs (i.e., the knee (p value = 0.040) and the toe (p value = 0.005)) were more likely to experience sensory dysfunction in the patients with internal capsule lesions. Hyperesthesia was more likely to occur in the thalamic patients, and hypoesthesia was more likely to occur in the patients with internal capsule lesions (p value < 0.001). In patients with thalamic lesions, Visual Analogue Scale (VAS) had a positive correlation with 5 Hz CPT on the shoulder (r = 0.010, p value = 0.005), 250 Hz CPT on the finger (r = 0.690, p value = 0.009) from the contralesional side, and 2000 Hz CPT on the knee (r = 0.690, p value = 0.009). In patients with internal capsule lesions, VAS had a positive correlation with 2000 Hz CPT on the knee (r = 0.312, p value = 0.039) and foot (r = 0.538, p value < 0.001). In conclusion, the abnormal fiber types, sensory dysfunction territory, and clinical signs of CPSP in thalamic stroke differ from those in internal capsule stroke. Implementation of the portable and convenient CPT protocol may help clarify the locations of different stroke lesions in various clinical settings.
电生理记录可量化不同部位引起的中枢性脑卒中后疼痛(CPSP)的临床特征。我们的目的是利用当前感知阈值(CPT)方法探讨CPSP患者的临床特征与病变位置之间的关系。在这里,患者在对侧和同侧的五个检测点进行了标准化的CPT测量,使用恒定的交流正弦波形刺激,频率为2000hz, 250hz和5hz。本横断面研究共招募了57例CPSP患者,其中丘脑病变13例,内囊病变44例。丘脑病变患者的a δ和C纤维异常发生率高于内囊病变患者(69.2%比36.4%,p值= 0.038;53.8% vs . 63.6%, p值= 0.038)。内囊病变患者Aβ纤维异常发生率高于丘脑病变患者(53.8%比63.6%,p值< 0.001)。丘脑病变患者感觉功能障碍多发生在上肢(即肩部(p值= 0.027)和手指(p值= 0.040))。内囊病变患者下肢(即膝关节(p值= 0.040)和脚趾(p值= 0.005))更容易出现感觉功能障碍。丘脑区患者更容易出现感觉亢进,内包膜病变患者更容易出现感觉低下(p值< 0.001)。丘脑病变患者视觉模拟评分(VAS)与肩部5hz CPT (r = 0.010, p值= 0.005)、对侧手指250hz CPT (r = 0.690, p值= 0.009)、膝关节2000hz CPT (r = 0.690, p值= 0.009)呈正相关。在有内囊病变的患者中,VAS评分与膝关节(r = 0.312, p值= 0.039)和足部(r = 0.538, p值< 0.001)2000 Hz CPT均呈正相关。综上所述,丘脑卒中的CPSP异常纤维类型、感觉功能障碍范围和临床体征与内囊卒中不同。实施便携方便的CPT方案可能有助于明确不同临床环境中不同脑卒中病变的位置。
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引用次数: 0
Performance Comparison of Different Neuroimaging Methods for Predicting Upper Limb Motor Outcomes in Patients after Stroke 不同神经影像学方法预测脑卒中患者上肢运动预后的性能比较
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-06-06 DOI: 10.1155/2022/4203698
Jingyan Tao, Zhaoqing Li, Yang Liu, Jianhua Li, Ruiliang Bai
Several neuroimaging methods have been proposed to assess the integrity of the corticospinal tract (CST) for predicting recovery of motor function after stroke, including conventional structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI). In this study, we aimed to compare the predicative performance of these methods using different neuroimaging modalities and optimize the prediction protocol for upper limb motor function after stroke in a clinical environment. We assessed 28 first-ever stroke patients with upper limb motor impairment. We used the upper extremity module of the Fugl-Meyer assessment (UE-FM) within 1 month of onset (baseline) and again 3 months poststroke. sMRI (T1- and T2-based) was used to measure CST-weighted lesion load (CST-wLL), and DTI was used to measure the fractional anisotropy asymmetry index (FAAI) and the ratio of fractional anisotropy (rFA). The CST-wLL within 1 month poststroke was closely correlated with upper limb motor outcomes and recovery potential. CST‐wLL ≥ 2.068 cc indicated serious CST damage and a poor outcome (100%). CST‐wLL < 1.799 cc was correlated with a considerable rate (>70%) of upper limb motor function recovery. CST-wLL showed a comparable area under the curve (AUC) to that of the CST-FAAI (p = 0.71). Inclusion of extra-CST-FAAI did not significantly increase the AUC (p = 0.58). Our findings suggest that sMRI-derived CST-wLL is a precise predictor of upper limb motor outcomes 3 months poststroke. We recommend this parameter as a predictive imaging biomarker for classifying patients' recovery prognosis in clinical practice. Conversely, including DTI appeared to induce no significant benefits.
已经提出了几种神经影像学方法来评估皮质脊髓束(CST)的完整性,以预测中风后运动功能的恢复,包括常规结构磁共振成像(sMRI)和弥散张量成像(DTI)。在这项研究中,我们旨在比较这些方法使用不同的神经成像方式的预测性能,并优化在临床环境中对中风后上肢运动功能的预测方案。我们评估了28例首次出现上肢运动障碍的中风患者。我们在发病1个月内(基线)和中风后3个月内使用Fugl-Meyer评估(UE-FM)的上肢模块。采用基于T1和t2的sMRI测量cst加权病变负荷(CST-wLL),采用DTI测量分数各向异性不对称指数(FAAI)和分数各向异性比率(rFA)。卒中后1个月内的CST-wLL与上肢运动预后和恢复潜力密切相关。CST‐wLL≥2.068 cc提示CST严重损伤,预后差(100%)。CST - wLL < 1.799 cc与上肢运动功能恢复率相当高(>70%)相关。CST-wLL的曲线下面积(AUC)与CST-FAAI相当(p = 0.71)。纳入extra-CST-FAAI未显著增加AUC (p = 0.58)。我们的研究结果表明,smri衍生的CST-wLL是中风后3个月上肢运动预后的精确预测指标。我们推荐该参数作为临床实践中对患者康复预后进行分类的预测性成像生物标志物。相反,包括DTI似乎没有显著的好处。
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引用次数: 3
Rapamycin Attenuates Anxiety and Depressive Behavior Induced by Helicobacter pylori in Association with Reduced Circulating Levels of Ghrelin 雷帕霉素减轻幽门螺杆菌诱导的焦虑和抑郁行为与胃饥饿素循环水平降低的关系
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-05-30 DOI: 10.1155/2022/2847672
J. Tian, Zeyu Wang, Yadi Ren, Yong Jiang, Ying Zhao, Man Li, Zhiguang Zhang
Background Helicobacter pylori (H. pylori) infection is closely associated with depression and development of neuroinflammation. The aim of this study is to explore the relationship between H. pylori, depression, and circulating levels of ghrelin. Methods Mice were randomly divided into three groups: healthy control group (gavaged sterile saline and injected with saline, n = 8); H. pylori+saline group (gavaged H. pylori and injected with saline, n = 8); and H. pylori+rapa group (gavaged H. pylori and injected with rapamycin, n = 8). Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used for anxiety and depressive behavior test. Western blotting was utilized to assess mTOR, p-mTOR, and GSMD expression, and serum ghrelin levels were estimated using ELISA. Results In the OFT, the control mice moved more and exhibited a increase in crossing number relative to the H. pylori+saline mice (all P < 0.05). Increased quantity of fecal boli can be indicative of increased anxiety and emotionality of the subject animal. H. pylori+saline mice exhibited an increase in fecal boli when compared to control mice and H. pylori+rapa mice (P < 0.05). H. pylori infected mice decreasing the expression of ghrelin. The protein levels of p-mTOR/mTOR in the gastric antrum mTOR signaling activation and low-level ghrelin in H. pylori-infect mice compared to those in control mice (all P <0.001). Compared with single H. pylori infection, mTOR inhibitors increased the ghrelin secretion of H. pylori infection to a certain extent (P < 0.05). The protein levels of GSDMD expression significantly increase in hippocampus of H. pylori-infected mice (P < 0.001). Rapamycin treatment inhibited expression of GSDMD in H. pylori-infected mice (P < 0.05). Conclusions H. pylori infection is associated with increased expression of mTOR and decreased circulating levels of ghrelin. Elevated pyroptosis in the brain and anxiety- and depressed-like behaviors occur when ghrelin levels are suppressed.
背景幽门螺杆菌感染与抑郁症和神经炎症的发生密切相关。本研究的目的是探讨幽门螺旋杆菌、抑郁症和胃饥饿素循环水平之间的关系。方法将小鼠随机分为3组:健康对照组(灌胃无菌生理盐水并注射生理盐水,n = 8);幽门螺杆菌+生理盐水组(灌胃幽门螺杆菌并注射生理盐水,n = 8);幽门螺杆菌+雷帕霉素组(灌胃幽门螺杆菌并注射雷帕霉素,n = 8)。焦虑和抑郁行为测试采用开放场试验(OFT)、蔗糖偏好试验(SPT)、强迫游泳试验(FST)和悬尾试验(TST)。Western blotting检测mTOR、p-mTOR和GSMD的表达,ELISA检测血清ghrelin水平。结果与幽门螺杆菌+生理盐水小鼠相比,对照组小鼠运动较多,交叉次数增加(P < 0.05)。粪粪数量的增加可能表明受试者动物的焦虑和情绪增加。与对照组和幽门螺杆菌+rapa小鼠相比,H. pylori+saline小鼠粪肠杆菌数量明显增加(P < 0.05)。幽门螺旋杆菌感染小鼠胃饥饿素表达降低。与对照组相比,幽门螺杆菌感染小鼠胃窦P -mTOR/mTOR蛋白水平、mTOR信号激活和低水平胃饥饿素(均P <0.001)。与单纯幽门螺杆菌感染相比,mTOR抑制剂在一定程度上增加了幽门螺杆菌感染的胃饥饿素分泌(P < 0.05)。幽门螺杆菌感染小鼠海马组织GSDMD蛋白表达水平显著升高(P < 0.001)。雷帕霉素抑制幽门螺杆菌感染小鼠GSDMD的表达(P < 0.05)。结论幽门螺杆菌感染与mTOR表达升高和胃饥饿素循环水平降低有关。当胃饥饿素水平受到抑制时,大脑中焦下垂的升高以及焦虑和抑郁样行为就会发生。
{"title":"Rapamycin Attenuates Anxiety and Depressive Behavior Induced by Helicobacter pylori in Association with Reduced Circulating Levels of Ghrelin","authors":"J. Tian, Zeyu Wang, Yadi Ren, Yong Jiang, Ying Zhao, Man Li, Zhiguang Zhang","doi":"10.1155/2022/2847672","DOIUrl":"https://doi.org/10.1155/2022/2847672","url":null,"abstract":"Background Helicobacter pylori (H. pylori) infection is closely associated with depression and development of neuroinflammation. The aim of this study is to explore the relationship between H. pylori, depression, and circulating levels of ghrelin. Methods Mice were randomly divided into three groups: healthy control group (gavaged sterile saline and injected with saline, n = 8); H. pylori+saline group (gavaged H. pylori and injected with saline, n = 8); and H. pylori+rapa group (gavaged H. pylori and injected with rapamycin, n = 8). Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used for anxiety and depressive behavior test. Western blotting was utilized to assess mTOR, p-mTOR, and GSMD expression, and serum ghrelin levels were estimated using ELISA. Results In the OFT, the control mice moved more and exhibited a increase in crossing number relative to the H. pylori+saline mice (all P < 0.05). Increased quantity of fecal boli can be indicative of increased anxiety and emotionality of the subject animal. H. pylori+saline mice exhibited an increase in fecal boli when compared to control mice and H. pylori+rapa mice (P < 0.05). H. pylori infected mice decreasing the expression of ghrelin. The protein levels of p-mTOR/mTOR in the gastric antrum mTOR signaling activation and low-level ghrelin in H. pylori-infect mice compared to those in control mice (all P <0.001). Compared with single H. pylori infection, mTOR inhibitors increased the ghrelin secretion of H. pylori infection to a certain extent (P < 0.05). The protein levels of GSDMD expression significantly increase in hippocampus of H. pylori-infected mice (P < 0.001). Rapamycin treatment inhibited expression of GSDMD in H. pylori-infected mice (P < 0.05). Conclusions H. pylori infection is associated with increased expression of mTOR and decreased circulating levels of ghrelin. Elevated pyroptosis in the brain and anxiety- and depressed-like behaviors occur when ghrelin levels are suppressed.","PeriodicalId":19122,"journal":{"name":"Neural Plasticity","volume":"42 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81143675","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
Anodal Transcranial Direct Current Stimulation (atDCS) of the Primary Motor Cortex (M1) Facilitates Nonconscious Error Correction of Negative Phase Shifts 初级运动皮层(M1)的阳极经颅直流电刺激(atDCS)促进负相移的无意识错误纠正
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-05-25 DOI: 10.1155/2022/9419154
B. Pollok, Martin Jurkiewicz, V. Krause
Accurate motor timing requires the temporally precise coupling between sensory input and motor output including the adjustment of movements with respect to changes in the environment. Such error correction has been related to a cerebello-thalamo-cortical network. At least partially distinct networks for the correction of perceived (i.e., conscious) as compared to nonperceived (i.e., nonconscious) errors have been suggested. While the cerebellum, the premotor, and the prefrontal cortex seem to be involved in conscious error correction, the network subserving nonconscious error correction is less clear. The present study is aimed at investigating the functional contribution of the primary motor cortex (M1) for both types of error correction in the temporal domain. To this end, anodal transcranial direct current stimulation (atDCS) was applied to the left M1 in a group of 18 healthy young volunteers during a resting period of 10 minutes. Sensorimotor synchronization as well as error correction of the right index finger was tested immediately prior to and after atDCS. Sham stimulation served as control condition. To induce error correction, nonconscious and conscious temporal step-changes were interspersed in a sequence of an isochronous auditory pacing signal in either direction (i.e., negative or positive) yielding either shorter or longer intervals. Prior to atDCS, faster error correction in conscious as compared to nonconscious trials was observed replicating previous findings. atDCS facilitated nonconscious error correction, but only in trials with negative step-changes yielding shorter intervals. In contrast to this, neither tapping speed nor synchronization performance with respect to the isochronous pacing signal was significantly modulated by atDCS. The data suggest M1 as part of a network distinctively contributing to the correction of nonconscious negative step-changes going beyond sensorimotor synchronization.
准确的电机定时要求在感官输入和电机输出之间的时间精确耦合,包括根据环境变化调整运动。这种错误纠正与小脑-丘脑-皮质网络有关。与非感知(即无意识)错误相比,已经提出了至少部分不同的用于纠正感知(即有意识)错误的网络。虽然小脑、前运动区和前额叶皮层似乎参与了有意识的错误纠正,但服务于无意识错误纠正的网络却不太清楚。本研究旨在探讨初级运动皮层(M1)在颞域中对两种类型的错误纠正的功能贡献。为此,18名健康青年志愿者在休息10分钟的时间内对左M1施加阳极经颅直流电刺激(atDCS)。在atDCS之前和之后立即测试了右手食指的感觉运动同步和纠错。假性刺激作为对照组。为了诱导错误纠正,在一个等时听觉起搏信号序列中(即,负或正)穿插无意识和有意识的时间阶跃变化,产生更短或更长的间隔。在atDCS之前,与无意识试验相比,在有意识试验中观察到更快的错误纠正,重复了先前的研究结果。atDCS促进了无意识错误纠正,但仅在负阶跃变化产生较短间隔的试验中。与此相反,atDCS对等时起搏信号的分拍速度和同步性能都没有显著调节。数据表明,M1是一个网络的一部分,特别有助于纠正超越感觉运动同步的无意识负阶跃变化。
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引用次数: 2
Brain Network Changes in Lumbar Disc Herniation Induced Chronic Nerve Roots Compression Syndromes 腰椎间盘突出症引起的慢性神经根压迫综合征的脑网络改变
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-05-14 DOI: 10.1155/2022/7912410
Yan-Peng Zhang, Guang-Hui Hong, Chuan-Yin Zhang
Lumbar disc herniation (LDH) induced nerve compression syndromes have been a prevalent problem with complex neural mechanisms. Changes in distributed brain areas are involved in the occurrence and persistence of syndromes. The present study aimed to investigate the changes of brain functional network in LDH patients with chronic sciatica using graph theory analysis. A total of thirty LDH adults presenting L4 and/or L5 root (s) compression syndromes (LDH group) and thirty age-, sex-, BMI- and education-matched healthy control (HC group) were recruited for functional MRI scan. Whole-brain functional network was constructed for each participant using Pearson's correlation. Global and nodal properties were calculated and compared between two groups, including small-worldness index, clustering coefficient, characteristic path length, degree centrality (DC), betweenness centrality (BC) and nodal efficiency. Both LDH and HC groups showed small-world architecture in the functional network of brain. However, LDH group showed that nodal centralities (DC, BC and nodal efficiency) increased in opercular part of inferior frontal gyrus; and decreased in orbital part of inferior frontal gyrus, lingual cortex and inferior occipital gyrus. The DC and efficiency in the right inferior occipital gyrus were negatively related with the Oswestry Disability Index in LDH group. In conclusion, the LDH-related chronic sciatica syndromes may induce regional brain alterations involving self-referential, emotional responses and pain regulation functions. But the whole-brain small-world architecture was not significantly disturbed. It may provide new insights into LDH patients with radicular symptoms from new perspectives.
腰椎间盘突出症(LDH)引起的神经压迫综合征一直是一个复杂的神经机制的普遍问题。分布脑区的变化与综合征的发生和持续有关。本研究旨在应用图论分析LDH合并慢性坐骨神经痛患者脑功能网络的变化。共招募了30例LDH成人L4和/或L5根压迫综合征(LDH组)和30例年龄、性别、BMI和教育程度相匹配的健康对照(HC组)进行功能性MRI扫描。采用Pearson相关法对每个参与者构建全脑功能网络。计算并比较两组的全局和节点属性,包括小世界指数、聚类系数、特征路径长度、度中心性(DC)、中间中心性(BC)和节点效率。LDH组和HC组脑功能网络均呈现小世界结构。LDH组显示下额回眼部节中度(DC、BC和节效率)升高;额下回眶部、舌皮层、枕下回均减少。LDH组右枕下回DC和效率与Oswestry失能指数呈负相关。总之,ldl相关的慢性坐骨神经痛综合征可能引起涉及自我参照、情绪反应和疼痛调节功能的大脑区域改变。但是整个大脑的小世界结构并没有受到明显的干扰。这可能从新的角度为LDH患者的神经根症状提供新的认识。
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引用次数: 2
Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice 长期环境富集缓解老年CD-1小鼠产前炎症诱导的功能障碍认知和突触蛋白水平
IF 3.1 4区 医学 Q2 Medicine Pub Date : 2022-05-06 DOI: 10.1155/2022/1483101
Zhe-Zhe Zhang, Li-ping Zeng, Jing Chen, Yong-Fang Wu, Ya-Tao Wang, Lan Xia, Qi-Gang Yang, Fang Wang, Gui-Hai Chen
A mounting body of evidence suggests that prenatal inflammation may enhance the rate of age-associated cognitive decline and may involve aberrant amounts of synaptic proteins in the hippocampus, including synaptotagmin-1 (Syt1) and activity-regulated cytoskeleton-associated protein (Arc). However, little is known about the specific impact of adolescent environmental enrichment (EE) on age-associated cognitive decline and the changes in synaptic proteins caused by prenatal inflammation. In this study, CD-1 mice in late pregnancy were given intraperitoneal doses of lipopolysaccharide (LPS, 50 μg/kg) or normal saline. Offspring arising from LPS dams were divided into a LPS group and a LPS plus EE (LPS-E) group. The LPS-E mice were exposed to EE from 2 months of age until the end of the experiment (3 or 15 months old). The Morris water maze (MWM) was used to assess the spatial learning and memory capacities of experimental mice, while western blotting and RNA-scope were used to determine the expression levels of Arc and Syt1 in the hippocampus at the protein and mRNA levels, respectively. Analysis revealed that at 15 months of age, the control mice experienced a reduction in cognitive ability and elevated expression levels of Arc and Syt1 genes when compared to control mice at 3 months of age. The LPS-E group exhibited better cognition and lower protein and mRNA levels of Arc and Syt1 than mice in the LPS group of the same age. However, the enriched environment mitigated but did not counteract, the effects of prenatal inflammation on cognitive and synaptic proteins when tested at either 3 or 15 months of age. Our findings revealed that long-term environmental enrichment improved the expression levels of synaptic proteins in CD-1 mice and that this effect was linked to the dysfunctional cognition caused by prenatal inflammation; this process may also be involved in the reduction of hippocampal Arc and Syt1 gene expression.
越来越多的证据表明,产前炎症可能会增加与年龄相关的认知能力下降的速度,并可能涉及海马中突触蛋白的异常数量,包括突触蛋白-1 (Syt1)和活动调节的细胞骨架相关蛋白(Arc)。然而,青少年环境富集(EE)对年龄相关认知能力下降和产前炎症引起的突触蛋白变化的具体影响知之甚少。在本研究中,CD-1孕晚期小鼠腹腔注射50 μg/kg的脂多糖(LPS)或生理盐水。将LPS母鼠分为LPS组和LPS + EE (LPS- e)组。LPS-E小鼠从2个月大开始暴露于EE,直到实验结束(3或15个月大)。采用Morris水迷宫(Morris water maze, MWM)评估实验小鼠的空间学习和记忆能力,采用western blotting和RNA-scope分别在蛋白和mRNA水平上检测Arc和Syt1在海马中的表达水平。分析显示,与3个月大的对照组小鼠相比,在15个月大时,对照小鼠的认知能力下降,Arc和Syt1基因的表达水平升高。与同龄LPS组相比,LPS- e组小鼠认知能力增强,Arc和Syt1蛋白及mRNA水平降低。然而,当在3个月或15个月大的时候测试时,丰富的环境减轻了但没有抵消产前炎症对认知和突触蛋白的影响。我们的研究结果表明,长期的环境富集改善了CD-1小鼠突触蛋白的表达水平,这种影响与产前炎症引起的认知功能障碍有关;这一过程也可能与海马Arc和Syt1基因表达的减少有关。
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引用次数: 7
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
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