Pub Date : 2024-06-05Epub Date: 2024-04-26DOI: 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.
{"title":"Effect of contextual prediction on emotional word processing: an evidence from ERPNR-D-24-00189.","authors":"Yulin Li, Xue Sui, Yutong Li","doi":"10.1097/WNR.0000000000002040","DOIUrl":"10.1097/WNR.0000000000002040","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869198","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}
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.
{"title":"Intervention of CXCL5 attenuated neuroinflammation and promoted neurological recovery after traumatic brain injury.","authors":"Leiyang Li, Jinpeng Zhou, Liying Han, Chengxuan Guo, Shuoyao Ma, Shunnan Ge, Yan Qu","doi":"10.1097/WNR.0000000000002032","DOIUrl":"10.1097/WNR.0000000000002032","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916819","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}
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.
{"title":"Nerolidol reduces depression-like behavior in mice and suppresses microglia activation by down-regulating DNA methyltransferase 1.","authors":"Guangcai Zhang, Xiaohui Zhou, Qifan Feng, Weihua Ke, Jiahui Pan, Haiying Zhang, Yixian Luan, Beibei Lei","doi":"10.1097/WNR.0000000000002029","DOIUrl":"10.1097/WNR.0000000000002029","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288593","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}
Pub Date : 2024-05-08Epub Date: 2024-03-15DOI: 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。
{"title":"Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats.","authors":"Fengwei Zheng, Weixin Li, Shaobo Su, Qiaoyan Hui","doi":"10.1097/WNR.0000000000002030","DOIUrl":"10.1097/WNR.0000000000002030","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288658","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}
Pub Date : 2024-05-08Epub Date: 2024-03-14DOI: 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.
{"title":"Inhibition of SIRT1 in the nucleus accumbens attenuates heroin addiction-related behavior by decreasing D1 neuronal autophagy.","authors":"Yanyan Huang, Meijun Liu, Zhiyao Zheng, Ruiping Lu, Chunlu Li, Min Su, Yixin Li, Baijuan Xia","doi":"10.1097/WNR.0000000000002033","DOIUrl":"10.1097/WNR.0000000000002033","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288592","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}
Pub Date : 2024-05-08Epub Date: 2024-03-12DOI: 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)。
{"title":"Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.","authors":"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","doi":"10.1097/WNR.0000000000002028","DOIUrl":"10.1097/WNR.0000000000002028","url":null,"abstract":"<p><p>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).</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288596","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}
Pub Date : 2024-04-17DOI: 10.1097/WNR.0000000000002035
Jian Wang, Diheng Gu, Ke Jin, Hualong Shen, Yaohua Qian
Intracerebral hemorrhage (ICH) is a fatal brain injury, but the current treatments for it are inadequate to reduce the severity of secondary brain injury. Our study aims to explore the molecular mechanism of Egr1 and Phlda1 in regulating hemin-induced neuronal pyroptosis, and hope to provide novel therapeutic targets for ICH treatment. Mouse hippocampal neuron cells treated with hemin were used to simulate an in-vitro ICH model. Using qRT-PCR and western blot to evaluate mRNA and protein concentrations. MTT assay was utilized to assess cell viability. LDH levels were determined by lactate Dehydrogenase Activity Assay Kit. IL-1β and IL-18 levels were examined by ELISA. The interaction of Egr1 and Phlda1 promoter was evaluated using chromatin immunoprecipitation and dual-luciferase reporter assays. Egr1 and Phlda1 were both upregulated in HT22 cells following hemin treatment. Hemin treatment caused a significant reduction in HT22 cell viability, an increase in Nlrc4 and HT22 cell pyroptosis, and heightened inflammation. However, knocking down Egr1 neutralized hemin-induced effects on HT22 cells. Egr1 bound to the promoter of Phlda1 and transcriptionally activated Phlda1. Silencing Phlda1 significantly reduced Nlrc4-dependent neuronal pyroptosis. Conversely, overexpressing Phlda1 mitigated the inhibitory effects of Egr1 knockdown on Nlrc4 and neuronal pyroptosis during ICH. Egr1 enhanced neuronal pyroptosis mediated by Nlrc4 under ICH via transcriptionally activating Phlda1.
{"title":"Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage.","authors":"Jian Wang, Diheng Gu, Ke Jin, Hualong Shen, Yaohua Qian","doi":"10.1097/WNR.0000000000002035","DOIUrl":"https://doi.org/10.1097/WNR.0000000000002035","url":null,"abstract":"Intracerebral hemorrhage (ICH) is a fatal brain injury, but the current treatments for it are inadequate to reduce the severity of secondary brain injury. Our study aims to explore the molecular mechanism of Egr1 and Phlda1 in regulating hemin-induced neuronal pyroptosis, and hope to provide novel therapeutic targets for ICH treatment. Mouse hippocampal neuron cells treated with hemin were used to simulate an in-vitro ICH model. Using qRT-PCR and western blot to evaluate mRNA and protein concentrations. MTT assay was utilized to assess cell viability. LDH levels were determined by lactate Dehydrogenase Activity Assay Kit. IL-1β and IL-18 levels were examined by ELISA. The interaction of Egr1 and Phlda1 promoter was evaluated using chromatin immunoprecipitation and dual-luciferase reporter assays. Egr1 and Phlda1 were both upregulated in HT22 cells following hemin treatment. Hemin treatment caused a significant reduction in HT22 cell viability, an increase in Nlrc4 and HT22 cell pyroptosis, and heightened inflammation. However, knocking down Egr1 neutralized hemin-induced effects on HT22 cells. Egr1 bound to the promoter of Phlda1 and transcriptionally activated Phlda1. Silencing Phlda1 significantly reduced Nlrc4-dependent neuronal pyroptosis. Conversely, overexpressing Phlda1 mitigated the inhibitory effects of Egr1 knockdown on Nlrc4 and neuronal pyroptosis during ICH. Egr1 enhanced neuronal pyroptosis mediated by Nlrc4 under ICH via transcriptionally activating Phlda1.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140692473","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}
Pub Date : 2024-04-17DOI: 10.1097/WNR.0000000000002039
C. Qi, Zhi Wen, Xin Huang
Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ± 4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ± 5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.
我们的目的是利用静息态功能磁共振成像(resting-state functional MRI)探讨甲状腺相关眼病(TAO)患者与健康对照组(HCs)之间初级视觉皮层(V1)内在功能连接(FC)模式的差异。21名TAO患者(14名男性和7名女性;平均年龄:54.17 ± 4.83岁)和21名匹配良好的HCs患者(14名男性和7名女性;平均年龄:55.17 ± 5.37岁)接受了静息态功能磁共振成像扫描。我们使用 FC 方法评估了 TAO 患者 V1 固有 FC 模式的改变。随后,通过支持向量机(SVM)方法,选择分析中发现的FC区域的改变作为分类特征,以区分TAO患者和HC患者。结果表明,与HCs相比,TAO患者左侧V1与双侧卡尔卡林(CAL)、舌回(LING)和枕上回之间,以及右侧V1与双侧CAL/LING和右侧小脑之间的FC值明显降低。此外,基于FC图的SVM分类模型在区分TAO患者和HC患者方面表现有效,使用左侧V1的FC达到了61.9%的准确率,使用右侧V1的FC达到了64.29%的准确率。我们的研究显示,TAO患者在休息时表现出V1和高级视觉区域之间的FC紊乱。这可能表明,TAO 患者的自上而下调节、视觉意象和视觉运动功能可能受损。这些见解对于理解TAO患者视力受损的潜在神经生物学机制可能很有价值。
{"title":"Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.","authors":"C. Qi, Zhi Wen, Xin Huang","doi":"10.1097/WNR.0000000000002039","DOIUrl":"https://doi.org/10.1097/WNR.0000000000002039","url":null,"abstract":"Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ± 4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ± 5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140693356","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}
Pub Date : 2024-04-12DOI: 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。
{"title":"The impact of physical exercise on hippocampal atrophy in mild cognitive impairment and Alzheimer's disease: a meta-analysis.","authors":"Gavin T Kress, Emily S Popa, David A Merrill, Jennifer E Bramen, Prabha Siddarth","doi":"10.1097/wnr.0000000000002037","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002037","url":null,"abstract":"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.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597795","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}
Pub Date : 2024-04-10DOI: 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.
{"title":"The polysaccharides from Balanophora polyandra enhanced neuronal autophagy to ameliorate brain function decline in natural aging mice through the PI3K/AKT/mTOR signaling pathway.","authors":"Wenyan Zhong, Jingjing Chen, Yumin He, Li Xiao, Chengfu Yuan","doi":"10.1097/wnr.0000000000002024","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002024","url":null,"abstract":"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.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597647","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}