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Effect of contextual prediction on emotional word processing: an evidence from ERPNR-D-24-00189. 语境预测对情绪化词语加工的影响:ERPNR-D-24-00189 的证据。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-06-05 Epub Date: 2024-04-26 DOI: 10.1097/WNR.0000000000002040
Yulin Li, Xue Sui, Yutong Li

Objective: This study examined the effect of context on the prediction of emotional words with varying valences. It investigated the neural mechanisms underlying the processing differences of emotion words with different valences in both predictable and unpredictable contexts. Additionally, it aimed to address the conflicting results regarding the processing time in predictive contexts reported in previous studies.

Methods: Participants were instructed to carefully read the text that included the specified emotion words. Event-related potentials elicited by emotional words were measured. To ensure that the participants can read the text carefully, 33% of the texts are followed by comprehension problems. After reading the text, the comprehension questions were answered based on the text content.

Results: The study revealed that the N400 amplitude elicited by an unpredictable context was greater than that elicited by a predictable context. Additionally, the N400 amplitude triggered by positive emotion words was larger than that triggered by negative emotion words. However, there was no significant difference in late positive component amplitude observed between contextual prediction and emotional word valence.

Conclusion: The present study suggests that predictive processing takes place at an intermediate stage of speech processing, approximately 400 ms after stimulus onset. Furthermore, the presence of a predictive context enhances the processing of emotional information. Notably, brain activity is more pronounced during the processing of positive emotional stimuli compared to negative emotional stimuli. Additionally, the facilitative effect of a predictable context diminishes in the advanced phase of Chinese speech comprehension.

研究目的本研究探讨了语境对预测不同情绪词的影响。它研究了在可预测和不可预测的语境中,不同价值的情绪词的处理差异的神经机制。此外,该研究还旨在解决以往研究中报告的有关预测语境中处理时间的矛盾结果:方法:指导受试者仔细阅读包含指定情绪词的文本。方法:指导受试者仔细阅读包含指定情绪词的文本,测量情绪词引起的事件相关电位。为确保受试者能仔细阅读文本,33%的文本后面会有理解问题。阅读文章后,根据文章内容回答理解问题:研究显示,不可预测的情境所引发的 N400 波幅大于可预测的情境所引发的 N400 波幅。此外,积极情绪词引发的 N400 波幅大于消极情绪词引发的 N400 波幅。然而,在晚期阳性成分振幅方面,情境预测和情绪词价值之间并无明显差异:本研究表明,预测加工发生在言语加工的中间阶段,即刺激开始后大约 400 毫秒。此外,预测性语境的存在会增强对情感信息的处理。值得注意的是,在处理积极情绪刺激时,大脑活动比处理消极情绪刺激时更为明显。此外,在中文语音理解的高级阶段,可预测语境的促进作用会减弱。
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引用次数: 0
Intervention of CXCL5 attenuated neuroinflammation and promoted neurological recovery after traumatic brain injury. 干预 CXCL5 可减轻神经炎症,促进创伤性脑损伤后的神经功能恢复。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-06-05 Epub Date: 2024-05-08 DOI: 10.1097/WNR.0000000000002032
Leiyang Li, Jinpeng Zhou, Liying Han, Chengxuan Guo, Shuoyao Ma, Shunnan Ge, Yan Qu

Neuroinflammation after traumatic brain injury (TBI) exhibits a strong correlation with neurological impairment, which is a crucial target for improving the prognosis of TBI patients. The involvement of CXCL5/CXCR2 signaling in the regulation of neuroinflammation in brain injury models has been documented. Therefore, the effects of CXCL5 on post-TBI neuroinflammation and its potential mechanisms need to be explored. Following TBI, C57BL/6 mice were administered intraperitoneal injections of a CXCL5 neutralizing antibody (Nab-CXCL5) (5 mg/kg, 2 times/day). Subsequently, the effects on neuroinflammation, nerve injury, and neurological function were assessed. Nab-CXCL5 significantly reduced the release of inflammatory factors, inhibited the formation of inflammatory microglia and astrocytes, and reduced the infiltration of peripheral immune cells in TBI mice. Additionally, this intervention led to a reduction in neuronal impairment and facilitated the restoration of sensorimotor abilities, as well as improvements in learning and memory functions. Peripheral administration of the Nab-CXCL5 to TBI mice could suppress neuroinflammation, reduce neurological damage, and improve neurological function. Our data suggest that neutralizing antibodies against CXCL5 (Nab-CXCL5) may be a promising agent for treating TBI.

创伤性脑损伤(TBI)后的神经炎症与神经功能损伤密切相关,是改善 TBI 患者预后的关键目标。在脑损伤模型中,CXCL5/CXCR2 信号传导参与了神经炎症的调控。因此,需要探索 CXCL5 对创伤后神经炎症的影响及其潜在机制。TBI 后,给 C57BL/6 小鼠腹腔注射 CXCL5 中和抗体(Nab-CXCL5)(5 毫克/千克,2 次/天)。随后,评估其对神经炎症、神经损伤和神经功能的影响。Nab-CXCL5 能明显减少 TBI 小鼠体内炎症因子的释放,抑制炎性小胶质细胞和星形胶质细胞的形成,并减少外周免疫细胞的浸润。此外,这种干预还能减少神经元损伤,促进感觉运动能力的恢复,并改善学习和记忆功能。给创伤性脑损伤小鼠外周注射 Nab-CXCL5 可抑制神经炎症,减少神经损伤,改善神经功能。我们的数据表明,针对 CXCL5 的中和抗体(Nab-CXCL5)可能是一种治疗创伤性脑损伤的有效药物。
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引用次数: 0
Caspase-1 deletion reveals pyroptosis participates in neural damage induced by cerebral ischemia/reperfusion in tMCAO model mice. Caspase-1缺失揭示了热蛋白沉积参与了tMCAO模型小鼠脑缺血/再灌注诱发的神经损伤。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-06-05 Epub Date: 2024-04-29 DOI: 10.1097/WNR.0000000000002041
Qing-Na Hao, Xiao-Bo Xue, Heng Zhou, Zhao-Li Hu

Pyroptosis, a form of programmed cell death, drives inflammation in the context of cerebral ischemia/reperfusion. The molecular mechanism of pyroptosis underlying ischemia/reperfusion, however, is not fully understood. The transient middle cerebral artery occlusion was applied to wild-type and caspase-1 knockout mice. 2,3,5-Triphenyltetrazolium chloride-staining and immunohistochemistry were used to identify the ischemic region, and western blot and immunofluorescence for the examination of neuronal pyroptosis. The expression of inflammatory factors and the behavioral function assessments were further conducted to examine the effects of caspase-1 knockout on protection against ischemia/reperfusion injury. Ischemia/reperfusion injury increased pyroptosis-related signals represented by the overexpression of pyroptosis-related proteins including caspase-1 and gasdermin D (GSDMD). Meanwhile, the number of GSDMD positive neurons increased in penumbra by immunofluorescence staining. Compared with wild-type mice, those with caspase-1 knockout exhibited decreased levels of pyroptosis-related proteins following ischemia/reperfusion. Furthermore, ischemia/reperfusion attack-induced brain infarction, cerebral edema, inflammatory factors, and neurological outcomes were partially improved in caspase-1 knockout mice. The data indicate that pyroptosis participates in ischemia/reperfusion induced-damage, and the caspase-1 might be involved, it provides some new insights into the molecular mechanism of ischemia.

在脑缺血/再灌注的情况下,嗜热细胞增多症(一种程序性细胞死亡)会引发炎症。然而,缺血/再灌注所引发的裂解热的分子机制尚未完全明了。对野生型小鼠和 caspase-1 基因敲除小鼠进行瞬时大脑中动脉闭塞实验。采用 2,3,5-三苯基氯化四氮唑染色法和免疫组化法确定缺血区域,并用 Western 印迹法和免疫荧光法检测神经元热解。为了研究caspase-1基因敲除对缺血再灌注损伤的保护作用,还进一步进行了炎症因子表达和行为功能评估。缺血/再灌注损伤增加了热蛋白沉积相关信号,表现为包括caspase-1和gasdermin D(GSDMD)在内的热蛋白沉积相关蛋白的过度表达。同时,通过免疫荧光染色,半影中 GSDMD 阳性神经元的数量增加。与野生型小鼠相比,caspase-1基因敲除的小鼠在缺血/再灌注后表现出热休克相关蛋白水平的下降。此外,缺血再灌注诱发的脑梗塞、脑水肿、炎症因子和神经系统结果在caspase-1基因敲除小鼠中得到了部分改善。这些数据表明,热蛋白沉积参与了缺血/再灌注诱导的损伤,而caspase-1可能参与其中,这为缺血的分子机制提供了一些新的见解。
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引用次数: 0
Nerolidol reduces depression-like behavior in mice and suppresses microglia activation by down-regulating DNA methyltransferase 1. 奈洛利多能减少小鼠的抑郁样行为,并通过下调 DNA 甲基转移酶 1 抑制小胶质细胞的激活。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-08 Epub Date: 2024-03-14 DOI: 10.1097/WNR.0000000000002029
Guangcai Zhang, Xiaohui Zhou, Qifan Feng, Weihua Ke, Jiahui Pan, Haiying Zhang, Yixian Luan, Beibei Lei

Modern medicine has unveiled that essential oil made from Aquilaria possesses sedative and hypnotic effects. Among the chemical components in Aquilaria, nerolidol, a natural sesquiterpene alcohol, has shown promising effects. This study aimed to unravel the potential of nerolidol in treating depression. Chronic unpredictable mild stress (CUMS) was utilized to induce depression-like behavior in mice, and open field test, sucrose preference, and tail suspension test was conducted. The impacts of nerolidol on the inflammatory response, microglial activation, and DNA methyltransferase 1 (DNMT1) were assessed. To study the regulatory role of DNMT1, lipopolysaccharide (LPS) was used to treat BV2 cells, followed by the evaluation of cell viability and DNMT1 level. Additionally, the influence of DNMT1 overexpression on BV2 cell activation was determined. Behavioral analysis revealed that nerolidol reduced depression-like behavior in mice. Nerolidol reduced the levels of inflammatory factors and microglial activation caused by CUMS. Nerolidol treatment was found to reduce DNMT1 levels in mouse brain tissue and it also decrease the LPS-induced increase in DNMT1 levels in BV2 cells. DNMT1 overexpression reversed the impacts of nerolidol on the inflammation response and cell activation. This study underscores the potential of nerolidol in reducing CUMS-induced depressive-like behavior and inhibiting microglial activation by downregulating DNMT1. These findings offer valuable insights into the potential of nerolidol as a therapeutic option for depression.

现代医学发现,水飞蓟精油具有镇静和催眠作用。在水飞蓟的化学成分中,天然倍半萜醇橙花醇具有良好的效果。本研究旨在揭示橙花叔醇治疗抑郁症的潜力。研究利用慢性不可预知轻度应激(CUMS)诱导小鼠的抑郁样行为,并进行了开阔地试验、蔗糖偏好和尾悬试验。评估了橙花醇对炎症反应、小胶质细胞活化和DNA甲基转移酶1(DNMT1)的影响。为了研究 DNMT1 的调控作用,使用脂多糖(LPS)处理 BV2 细胞,然后评估细胞活力和 DNMT1 水平。此外,还测定了 DNMT1 过表达对 BV2 细胞活化的影响。行为分析表明,橙花叔醇减少了小鼠的抑郁样行为。奈洛利多降低了CUMS引起的炎症因子水平和小胶质细胞活化。研究发现,奈洛利多能降低小鼠脑组织中的 DNMT1 水平,还能降低 LPS 诱导的 BV2 细胞中 DNMT1 水平的升高。DNMT1 的过表达逆转了橙花醇对炎症反应和细胞活化的影响。这项研究强调了橙花醇通过下调 DNMT1 在减少 CUMS 诱导的抑郁样行为和抑制小胶质细胞活化方面的潜力。这些发现为将橙花醇作为抑郁症治疗药物的潜力提供了宝贵的见解。
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引用次数: 0
Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats. Annexin A1 在大鼠弥漫性轴突损伤中通过抑制氧化应激传递神经保护功能
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-08 Epub Date: 2024-03-15 DOI: 10.1097/WNR.0000000000002030
Fengwei Zheng, Weixin Li, Shaobo Su, Qiaoyan Hui

Diffuse axonal injury (DAI) is a critical pathological facet of traumatic brain injury (TBI). Oxidative stress plays a significant role in the progress of DAI. Annexin A1 (AnxA1) has been demonstrated to benefit from recovery of neurofunctional outcomes after TBI. However, whether AnxA1 exhibits neuronal protective function by modulating oxidative stress in DAI remains unknown. Expression of AnxA1 was evaluated via real-time PCR and western blotting in rat brainstem after DAI. The neurological effect of AnxA1 following DAI through quantification of modified neurologic severity score (mNSS) was compared between wild-type and AnxA1-knockout rats. Brain edema and neuronal apoptosis, as well as expression of oxidative factors and inflammatory cytokines, were analyzed between wild-type and AnxA1 deficiency rats after DAI. Furthermore, mNSS, oxidative and inflammatory cytokines were assayed after timely administration of recombinant AnxA1 for DAI rats. In the brainstem of DAI, the expression of AnxA1 remarkably increased. Ablation of AnxA1 increased the mNSS score and brain water content of rats after DAI. Neuron apoptosis in the brainstem after DAI was exaggerated by AnxA1 deficiency. In addition, AnxA1 deficiency significantly upregulated the level of oxidative and inflammatory factors in the brainstem of DAI rats. Moreover, mNSS decreased by AnxA1 treatment in rats following DAI. Expression of oxidative and inflammatory molecules in rat brainstem subjected to DAI inhibited by AnxA1 administration. AnxA1 exhibited neuronal protective function in the progression of DAI mainly dependent on suppressing oxidative stress and inflammation.

弥漫性轴索损伤(DAI)是创伤性脑损伤(TBI)的一个重要病理特征。氧化应激在弥漫性轴索损伤的进展过程中起着重要作用。事实证明,Annexin A1(AnxA1)有利于创伤性脑损伤后神经功能的恢复。然而,AnxA1 是否通过调节 DAI 中的氧化应激而发挥保护神经元的功能仍是未知数。我们通过实时 PCR 和 Western 印迹技术评估了 AnxA1 在 DAI 后大鼠脑干中的表达。通过量化改良神经系统严重程度评分(mNSS),比较了野生型大鼠和 AnxA1 基因敲除大鼠在 DAI 后 AnxA1 对神经系统的影响。分析了野生型大鼠和 AnxA1 基因缺失大鼠在 DAI 后的脑水肿、神经细胞凋亡以及氧化因子和炎症细胞因子的表达情况。此外,在给 DAI 大鼠及时注射重组 AnxA1 后,还检测了 mNSS、氧化因子和炎性细胞因子。在 DAI 大鼠的脑干中,AnxA1 的表达明显增加。消融 AnxA1 增加了 DAI 大鼠的 mNSS 评分和脑水含量。AnxA1 缺乏会加重 DAI 后脑干神经元的凋亡。此外,缺乏 AnxA1 会显著上调 DAI 大鼠脑干中氧化和炎症因子的水平。此外,大鼠脑干损伤后,经 AnxA1 处理,mNSS 水平下降。给予 AnxA1 可抑制 DAI 大鼠脑干中氧化和炎症分子的表达。AnxA1在DAI进展过程中对神经元的保护功能主要依赖于抑制氧化应激和炎症。
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引用次数: 0
Inhibition of SIRT1 in the nucleus accumbens attenuates heroin addiction-related behavior by decreasing D1 neuronal autophagy. 通过减少 D1 神经元的自噬,抑制伏隔核中的 SIRT1 可减轻与海洛因成瘾相关的行为。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-08 Epub Date: 2024-03-14 DOI: 10.1097/WNR.0000000000002033
Yanyan Huang, Meijun Liu, Zhiyao Zheng, Ruiping Lu, Chunlu Li, Min Su, Yixin Li, Baijuan Xia

This study aimed to investigate the effects of SIRT1 modulation on heroin addiction-like behavior and its possible biological mechanisms. Wild-type C57BL/6J and Sirt1loxp/loxp D1-Cre mice were used in this experiment, and Sirt1 loxp/loxp D1-Cre(-) mice were used as a control for conditional knockout mice. Mice were divided into saline control and heroin-dependent groups. Behavioral methods were used to record the withdrawal response, conditioned place preference (CPP) changes, and open field test results. Transmission electron microscopy (TEM) was used to observe the structure of autophagosomes in nucleus accumbens (NAc) neurons. The expression of SIRT1 and autophagy-related proteins and genes, such as LC3Ⅱ, ATG5 , and ATG7 , was detected in the NAc of each mouse group via western blot, real-time quantitative PCR (qPCR) analyzes, and immunofluorescence. The results of this experiment showed that compared with the saline group, mice in the wild-type heroin-dependent group showed marked withdrawal symptoms, with more autophagosomes observed in NAc via TEM. Compared with wild-type and Sirt1loxp/loxp D1-Cre(-) heroin-dependent groups, CPP formation was found to be reduced in the conditional knockout mouse group, with a significant decrease in spontaneous activity. Western blot, qPCR, and immunofluorescence results indicated that the expression of LC3Ⅱ, ATG-5, and ATG-7 was significantly reduced in the NAc of the Sirt1loxp/loxp D1-Cre(+) group. It was still, however, higher than that in the saline control group. These results suggest that inhibition of Sirt1 expression may prevent heroin-induced addiction-related behaviors via reducing D1 neuronal autophagy.

本研究旨在探讨调节SIRT1对海洛因成瘾样行为的影响及其可能的生物学机制。本实验使用野生型 C57BL/6J 和 Sirt1loxp/loxpD1-Cre 小鼠,Sirt1loxp/loxpD1-Cre(-) 小鼠作为条件性基因敲除小鼠的对照。小鼠被分为生理盐水对照组和海洛因依赖组。采用行为学方法记录戒断反应、条件性场所偏好(CPP)变化和开阔地测试结果。透射电子显微镜(TEM)用于观察神经核(NAc)中自噬体的结构。通过Western印迹、实时定量PCR(qPCR)分析和免疫荧光检测了各组小鼠NAc中SIRT1和自噬相关蛋白和基因(如LC3Ⅱ、ATG5和ATG7)的表达。实验结果表明,与生理盐水组相比,野生型海洛因依赖组小鼠表现出明显的戒断症状,通过TEM在NAc中观察到更多的自噬体。与野生型和Sirt1loxp/loxpD1-Cre(-)海洛因依赖组相比,条件性基因敲除小鼠组的CPP形成减少,自发活动显著降低。Western印迹、qPCR和免疫荧光结果表明,在Sirt1loxp/loxpD1-Cre(+)组的NAc中,LC3Ⅱ、ATG-5和ATG-7的表达明显减少。但仍高于生理盐水对照组。这些结果表明,抑制Sirt1的表达可通过减少D1神经元自噬防止海洛因诱发的成瘾相关行为。
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引用次数: 0
Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients. 人尿凯利苷原酶对急性缺血性中风患者皮质脊髓束损伤的保护作用
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-08 Epub Date: 2024-03-12 DOI: 10.1097/WNR.0000000000002028
Peifang Li, Honglin Lu, Xiaoman Shi, Jiajia Yan, Lixia Zhou, Jipeng Yang, Binbin Wang, Yanying Zhao, Luji Liu, Yipu Zhu, Lei Xu, Xiaoli Yang, Xudong Su, Yi Yang, Tong Zhang, Li Guo, Xiaoyun Liu

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P  < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P <  0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P  < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).

本研究旨在评估人尿凯利苷原酶(HUK)对急性缺血性脑卒中(AIS)患者运动功能预后和皮质脊髓束恢复的影响。该研究是一项随机对照单盲试验。80 名 AIS 患者被分为两组:HUK 组和对照组。HUK 组接受 HUK 和标准治疗,而对照组只接受标准治疗。入院和出院时,对美国国立卫生研究院卒中量表(NIHSS)、巴特尔指数(BI)和肌肉力量进行评分。主要终点是AIS患者在不同治疗方法下的短期疗效。次要终点是不同治疗方法对皮质脊髓束纤维的损伤程度。与对照组相比,HUK 组的 NIHSS 量表、BI 和肌力评分均有明显改善(Mann-Whitney U 检验;P<0.05)。
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引用次数: 0
The impact of physical exercise on hippocampal atrophy in mild cognitive impairment and Alzheimer's disease: a meta-analysis. 体育锻炼对轻度认知障碍和阿尔茨海默氏症患者海马体萎缩的影响:一项荟萃分析。
IF 1.7 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-12 DOI: 10.1097/wnr.0000000000002037
Gavin T Kress, Emily S Popa, David A Merrill, Jennifer E Bramen, Prabha Siddarth
Physical activity (PA) is a promising therapeutic for Alzheimer's disease (AD). Only a handful of meta-analyses have studied the impact of PA interventions on regional brain volumes, and none to date has solely included studies on effect of PA on regional brain volumes in individuals with cognitive impairment (CI). In this meta-analysis, we examined whether there is support for the hypothesis that PA interventions positively impact hippocampal volume (HV) in individuals with CI. We also assessed whether the level of CI [mild CI (MCI) vs. AD] impacted this relationship. We identified six controlled trials that met inclusion criteria. These included 236 participants with AD, MCI, or preclinical AD. Data were extracted and analyzed following Cochrane guidelines. We used a random-effects model to estimate the mean change in HV pre- and post-exercise intervention. Forest plots, Hedges' g funnel plots, and Egger's test were used to assess unbiasedness and visualize intervention effects, and Tau2, Cochran's Q, and I2 were calculated to assess heterogeneity. The primary analysis revealed a significant positive effect of PA on total HV. However, sub-group analyses indicated a significant preservation of HV only in individuals with MCI, but not in those with AD. Egger's test indicated no evidence of publication bias. Subgroup analyses also revealed significant heterogeneity only within the MCI cohort for the total and left HV. PA demonstrated a moderate, significant effect in preserving HV among individuals with MCI, but not AD, highlighting a therapeutic benefit, particularly in earlier disease stages.
体力活动(PA)是一种治疗阿尔茨海默病(AD)的有效方法。只有少数荟萃分析研究了体育锻炼干预对区域脑容量的影响,迄今为止还没有一项荟萃分析只研究了体育锻炼对认知障碍(CI)患者区域脑容量的影响。在这项荟萃分析中,我们研究了 PA 干预对 CI 患者海马体积(HV)产生积极影响的假设是否得到支持。我们还评估了 CI 的程度 [轻度 CI (MCI) vs. AD] 是否会影响这种关系。我们确定了六项符合纳入标准的对照试验。其中包括 236 名患有注意力缺失症、MCI 或临床前注意力缺失症的参与者。我们按照 Cochrane 指南对数据进行了提取和分析。我们使用随机效应模型来估算运动干预前后 HV 的平均变化。森林图、Hedges'g 漏斗图和 Egger's 检验用于评估无偏性和可视化干预效果,Tau2、Cochran's Q 和 I2 用于评估异质性。主要分析显示,PA 对总 HV 有明显的积极影响。然而,亚组分析表明,只有 MCI 患者的 HV 有明显的保护作用,而 AD 患者则没有。Egger检验表明没有证据表明存在发表偏倚。亚组分析还显示,只有在MCI队列中,总HV和左侧HV存在显著异质性。PA在保护MCI患者的HV方面具有中等程度的显着效果,但在AD患者中却不明显,这凸显了其治疗效果,尤其是在疾病的早期阶段。
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引用次数: 0
The polysaccharides from Balanophora polyandra enhanced neuronal autophagy to ameliorate brain function decline in natural aging mice through the PI3K/AKT/mTOR signaling pathway. Balanophora polyandra多糖通过PI3K/AKT/mTOR信号通路增强神经元自噬,从而改善自然衰老小鼠的脑功能衰退。
IF 1.7 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-10 DOI: 10.1097/wnr.0000000000002024
Wenyan Zhong, Jingjing Chen, Yumin He, Li Xiao, Chengfu Yuan
The decline of aging brain neurons is the main cause of various neurodegenerative disease. This study aimed to examine the impact of Balanophora polyandra polysaccharides (BPP) against aging related neuronal deterioration. C57BL/6 mice were fed with regular feed for 27 months to establish a natural aging mouse model. From 3 months of age, mice in the drug-treated group were respectively fed with feed containing 0.05 or 0.18% BPP until 27 months of age. The effects of BPP treatment on the pathological changes of neurons in mice brain were evaluated, as well as autophagy-related and signaling pathway proteins. BPP treatment had a notable positive impact on the pathological injury of cortical and hippocampal neurons, alleviated neuronal degeneration, and enhanced the staining of Nissl bodies in natural aging mice. Furthermore, BPP upregulated autophagy-related proteins LC3 II/I, Parkin, and PINK1 in the cortex and hippocampus of aging mice, and significantly decreased the expression of p62, PI3K, p-protein Kinase B (AKT), and p-mTOR. Immunofluorescence results showed a reduction in the brightness of LC3, which mainly coexpressed with NeuN in natural aging mice brain, and increased LC3-positive neurons were observed after BPP treatment. Collectively, BPP treatment enhanced neuronal autophagy to improve brain functional degradation through the PI3K/AKT/mTOR signaling in natural aging mice. These finding suggested that BPP has potential to mitigate or delay the neurodegeneration associated with aging and further investigation was needed to validate its efficacy in elderly populations.
大脑神经元衰退是各种神经退行性疾病的主要原因。本研究旨在探讨巴兰多糖(BPP)对衰老相关神经元退化的影响。用常规饲料喂养 C57BL/6 小鼠 27 个月,以建立自然衰老小鼠模型。从 3 个月大开始,药物治疗组的小鼠分别用含 0.05% 或 0.18% BPP 的饲料喂养至 27 个月大。评估了 BPP 治疗对小鼠大脑神经元病理变化的影响,以及自噬相关蛋白和信号通路蛋白的影响。BPP治疗对自然衰老小鼠大脑皮层和海马神经元的病理损伤有显著的积极影响,缓解了神经元变性,增强了Nissl体的染色。此外,BPP还能上调衰老小鼠皮层和海马中的自噬相关蛋白LC3 II/I、Parkin和PINK1,并显著降低p62、PI3K、p-蛋白激酶B(AKT)和p-mTOR的表达。免疫荧光结果显示,自然衰老小鼠脑中主要与NeuN共表达的LC3亮度降低,而BPP治疗后观察到LC3阳性神经元增加。总之,BPP治疗可通过PI3K/AKT/mTOR信号转导增强神经元自噬,从而改善自然衰老小鼠的脑功能退化。这些发现表明,BPP 有可能减轻或延缓与衰老相关的神经退行性病变,但还需要进一步研究以验证其在老年人群中的疗效。
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引用次数: 0
ADAMTS13 deficiency exacerbates neuroinflammation by targeting matrix metalloproteinase-9 in ischemic brain injury. 缺血性脑损伤中,ADAMTS13的缺乏会通过靶向基质金属蛋白酶-9加剧神经炎症。
IF 1.7 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-10 DOI: 10.1097/wnr.0000000000002017
Hongxiang Jiang, Juntao Hu, Peidong He, Yu Wu, Fei Li, Qianxue Chen
Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.
我们的设计旨在探索基质金属蛋白酶-9(MMP-9)可能参与急性缺血性中风(AIS)相关炎症反应的情况。我们还旨在初步研究具有血栓疏松素 I 型重复序列的崩解素样金属蛋白酶-13(ADAMTS13)对 AIS 中 MMP-9 的潜在影响。我们建立了小胶质细胞缺氧-葡萄糖模型和大脑中动脉闭塞(MCAO)的 AIS 小鼠模型。我们用 Western 印迹(WB)和实时定量 PCR 评估了体内和体外 MMP-9 的表达模式。MMP-9的下调是通过使用ACE抑制剂(如曲妥普利)实现的。在 MCAO 模型中,我们使用了 ADAMTS13 缺陷小鼠。然后,我们评估了相关的神经功能评分、脑水肿和梗死体积。我们使用 WB 评估了 COX2 和 iNOS 等炎症相关蛋白的水平,并通过酶联免疫吸附试验测定了体内炎症细胞因子的表达。我们的研究结果表明,在 MCAO 模型中,MMP-9 上调,而 ADAMTS13 下调。抑制MMP-9可减少炎症和缺血性脑损伤。在小鼠 AIS 模型中,ADAMTS13 可预防脑损伤、改善神经功能并减少炎症反应。此外,ADAMTS13还能减轻MMP-9诱导的体内神经炎症。研究表明,ADAMTS13 缺乏会通过 MMP-9 依赖性炎症机制加剧缺血性脑损伤。因此,ADAMTS13-MMP-9轴可能具有治疗AIS的潜力。
{"title":"ADAMTS13 deficiency exacerbates neuroinflammation by targeting matrix metalloproteinase-9 in ischemic brain injury.","authors":"Hongxiang Jiang, Juntao Hu, Peidong He, Yu Wu, Fei Li, Qianxue Chen","doi":"10.1097/wnr.0000000000002017","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002017","url":null,"abstract":"Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"70 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597691","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}
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