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":" ","pages":"431-438"},"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 : 2024-04-12DOI: 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":"243 1","pages":""},"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":"243 1","pages":""},"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}
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.
{"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}
Pub Date : 2024-04-10DOI: 10.1097/wnr.0000000000002031
Zhang Zhi, Xiao Liang, Muhua Huang, Lin Wu, Fuqing Zhou
The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.
{"title":"The association between glymphatic system dysfunction and alterations in cerebral function and structure in patients with white matter hyperintensities.","authors":"Zhang Zhi, Xiao Liang, Muhua Huang, Lin Wu, Fuqing Zhou","doi":"10.1097/wnr.0000000000002031","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002031","url":null,"abstract":"The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"102 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597650","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 : 2024-04-08DOI: 10.1097/wnr.0000000000002036
Lingyi Huang, Ding Bai, Xiaojuan Su
Transfer RNAs (tRNAs) can regulate cell behavior and are associated with neurological disorders. Here, we aimed to investigate the expression levels of tRNAs in oligodendrocyte precursor cells (OPCs) and their possible roles in the regulation of brain white matter injury (WMI). Newborn Sprague-Dawley rats (postnatal day 5) were used to establish a model that mimicked neonatal brain WMI. RNA-array analysis was performed to examine the expression of tRNAs in OPCs. psRNAtarget software was used to predict target mRNAs of significantly altered tRNAs. Gene ontology (GO) and KEGG were used to analyze the pathways for target mRNAs. Eighty-nine tRNAs were changed after WMI (fold change absolute ≥1.5, P < 0.01), with 31 downregulated and 58 upregulated. Among them, three significantly changed tRNAs were identified, with two being significantly increased (chr10.trna1314-ProTGG and chr2.trna2771-ProAGG) and one significantly decreased (chr10.trna11264-GlyTCC). Further, target mRNA prediction and GO/KEGG pathway analysis indicated that the target mRNAs of these tRNAs are mainly involved in G-protein coupled receptor signaling pathways and beta-alanine metabolism, which are both related to myelin formation. In summary, the expression of tRNAs in OPCs was significantly altered after brain WMI, suggesting that tRNAs may play important roles in regulating WMI. This improves the knowledge about WMI pathophysiology and may provide novel treatment targets for WMI.
{"title":"Altered expression of transfer RNAs and their possible roles in brain white matter injury.","authors":"Lingyi Huang, Ding Bai, Xiaojuan Su","doi":"10.1097/wnr.0000000000002036","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002036","url":null,"abstract":"Transfer RNAs (tRNAs) can regulate cell behavior and are associated with neurological disorders. Here, we aimed to investigate the expression levels of tRNAs in oligodendrocyte precursor cells (OPCs) and their possible roles in the regulation of brain white matter injury (WMI). Newborn Sprague-Dawley rats (postnatal day 5) were used to establish a model that mimicked neonatal brain WMI. RNA-array analysis was performed to examine the expression of tRNAs in OPCs. psRNAtarget software was used to predict target mRNAs of significantly altered tRNAs. Gene ontology (GO) and KEGG were used to analyze the pathways for target mRNAs. Eighty-nine tRNAs were changed after WMI (fold change absolute ≥1.5, P < 0.01), with 31 downregulated and 58 upregulated. Among them, three significantly changed tRNAs were identified, with two being significantly increased (chr10.trna1314-ProTGG and chr2.trna2771-ProAGG) and one significantly decreased (chr10.trna11264-GlyTCC). Further, target mRNA prediction and GO/KEGG pathway analysis indicated that the target mRNAs of these tRNAs are mainly involved in G-protein coupled receptor signaling pathways and beta-alanine metabolism, which are both related to myelin formation. In summary, the expression of tRNAs in OPCs was significantly altered after brain WMI, suggesting that tRNAs may play important roles in regulating WMI. This improves the knowledge about WMI pathophysiology and may provide novel treatment targets for WMI.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"69 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597780","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}
Wnt signaling plays an important role in adult brain function, and its dysregulation has been implicated in the loss of neuronal homeostasis. Despite the existence of many studies on the participation of the Wnt pathway in adult neurons, its regulation in astrocytes has been scarcely explored. Several reports point to the presence of Wnt ligands in astrocytes and their possible impact on neuronal plasticity or neuronal death. We aimed to analyze the effect of the neurotransmitter glutamate and the inflammatory cytokine TNFα on the mRNA and protein levels of the canonical Wnt agonist Wnt7a and the antagonist Dkk1 in cultured astrocytes. Primary astrocyte cultures from rat cerebral cortices were exposed to glutamate or TNFα. Wnt7a and Dkk1 expression was analyzed by RT-qPCR and its protein abundance and distribution was assessed by immunofluorescence. We found high basal expression and protein levels of Wnt7a and Dkk1 in unstimulated astrocytes and overproduction of Dkk1 mRNA induced by the two stimuli. These results reveal the astrocytic source of the canonical Wnt ligands Wnt7a and Dkk1, whose levels are differentially regulated by glutamate and TNFα. Astrocytes are a significant source of Wnt ligands, the production of which can be differentially regulated under excitatory or proinflammatory conditions, thereby impacting neuronal function.
{"title":"Differential changes in Wnt7 and Dkk1 levels in astrocytes exposed to glutamate or TNFα.","authors":"Lizbeth García-Velázquez, Reem Alobayan, Denisse Morales-Moreno, Evangelina Ávila-Muñoz, Clorinda Arias","doi":"10.1097/wnr.0000000000002038","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002038","url":null,"abstract":"Wnt signaling plays an important role in adult brain function, and its dysregulation has been implicated in the loss of neuronal homeostasis. Despite the existence of many studies on the participation of the Wnt pathway in adult neurons, its regulation in astrocytes has been scarcely explored. Several reports point to the presence of Wnt ligands in astrocytes and their possible impact on neuronal plasticity or neuronal death. We aimed to analyze the effect of the neurotransmitter glutamate and the inflammatory cytokine TNFα on the mRNA and protein levels of the canonical Wnt agonist Wnt7a and the antagonist Dkk1 in cultured astrocytes. Primary astrocyte cultures from rat cerebral cortices were exposed to glutamate or TNFα. Wnt7a and Dkk1 expression was analyzed by RT-qPCR and its protein abundance and distribution was assessed by immunofluorescence. We found high basal expression and protein levels of Wnt7a and Dkk1 in unstimulated astrocytes and overproduction of Dkk1 mRNA induced by the two stimuli. These results reveal the astrocytic source of the canonical Wnt ligands Wnt7a and Dkk1, whose levels are differentially regulated by glutamate and TNFα. Astrocytes are a significant source of Wnt ligands, the production of which can be differentially regulated under excitatory or proinflammatory conditions, thereby impacting neuronal function.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"67 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597642","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}
Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.
脑出血（ICH）是一种严重的中风亚型。继发性损伤是导致 ICH 后神经功能缺损的关键因素。电针（EA）可以改善 ICH 后的神经功能，但其内在机制尚不清楚。本研究旨在探讨电针能否通过抗氧化应激改善 ICH 后的继发性损伤及其潜在的调节机制。通过向大鼠纹状体注射自体血，建立了大鼠 ICH 模型。EA和EA联合过氧化物酶体增殖激活受体-γ（PPARγ）阻断剂干预后，Zea-longa评分、改良神经系统严重程度评分和野外开放试验用于评估大鼠的神经功能。流式细胞术检测组织活性氧（ROS）水平。组织肿瘤坏死因子-α（TNF-α）水平通过酶联免疫吸附试验进行分析。用 Western 印迹法检测 PPAR γ、核因子红细胞相关因子 2（Nrf2）和γ-谷氨酰半胱氨酸合成酶（γ-GCS）的蛋白表达。免疫组化用于观察小胶质细胞的活化。透射电子显微镜观察轴突髓鞘的脱髓鞘程度。与模型组相比，EA干预改善了神经功能，降低了ROS和TNF-α水平，增加了PPARγ、Nrf2和γ-GCS的蛋白表达，降低了小胶质细胞的活化，还减轻了轴突髓鞘的损伤。此外，PPARγ阻断剂可部分减弱EA的神经保护作用。EA能改善大鼠ICH后继发性损伤的神经功能，可能是通过激活PPARγ/Nrf2/γ-GCS信号通路、减少小胶质细胞活化和抑制氧化应激，从而减轻轴突脱髓鞘的程度发挥了作用。
{"title":"Electroacupuncture reduces oxidative stress response and improves secondary injury of intracerebral hemorrhage in rats by activating the peroxisome proliferator-activated receptor-γ/nuclear factor erythroid2-related factor 2/γ-glutamylcysteine synthetase pathway.","authors":"Weigang Luo, Wei Bu, Hequn Chen, Wanhu Liu, Xudong Lu, Guisong Zhang, Cuicui Liu, Xiaohui Li, Huiling Ren","doi":"10.1097/wnr.0000000000002026","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002026","url":null,"abstract":"Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"20 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597689","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 : 2024-04-08DOI: 10.1097/wnr.0000000000002034
Shimei Li, Songjiang Tang, Lina Dai, Zhonglu Jian, Xi Li
The objective of this study is to disclose the role of emodin, a natural anthraquinone derivative that has been proposed to suppress microglial activation and inflammation, in morphine tolerance. Here, cell counting kit-8 method assayed the viability of BV2 microglial cells treated by ascending concentrations of emodin. In emodin-pretreated BV2 microglial cells challenged with morphine with or without transfection of toll-like receptor 4 (TLR4) overexpression plasmids, transwell assay measured cell migration. Immunofluorescence staining and western blot detected the expression of microglial markers. Inflammatory levels were subjected to ELISA and western blot. BODIPY 581/591 C11 assay estimated lipid reactive oxygen species activity. Iron assay kit examined total iron content. Western blot tested the expression of ferroptosis- and TLR4/nuclear factor-kappaB (NF-κB)/NOD-like receptor 3 (NLRP3) pathway-associated proteins. Molecular docking predicted the binding affinity of emodin to TLR4. Emodin was noted to obstruct the migration, activation, inflammatory response, and ferroptosis of BV2 microglial cells induced by morphine. In addition, emodin had a high binding affinity with TLR4 and inactivated TLR4/NF-κB/NLRP3 pathway in morphine-challenged BV2 microglial cells. Upregulation of TLR4 partially countervailed the protective role of emodin against morphine-elicited BV2 microglial cell migration, activation, inflammation, and ferroptosis. Accordingly, emodin might target TLR4 and act as an inactivator of TLR4/NF-κB/NLRP3 pathway, thus inhibiting BV2 microglial activation and inflammation to mitigate morphine tolerance.
{"title":"Emodin relieves morphine-stimulated BV2 microglial activation and inflammation through the TLR4/NF-κB/NLRP3 pathway.","authors":"Shimei Li, Songjiang Tang, Lina Dai, Zhonglu Jian, Xi Li","doi":"10.1097/wnr.0000000000002034","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002034","url":null,"abstract":"The objective of this study is to disclose the role of emodin, a natural anthraquinone derivative that has been proposed to suppress microglial activation and inflammation, in morphine tolerance. Here, cell counting kit-8 method assayed the viability of BV2 microglial cells treated by ascending concentrations of emodin. In emodin-pretreated BV2 microglial cells challenged with morphine with or without transfection of toll-like receptor 4 (TLR4) overexpression plasmids, transwell assay measured cell migration. Immunofluorescence staining and western blot detected the expression of microglial markers. Inflammatory levels were subjected to ELISA and western blot. BODIPY 581/591 C11 assay estimated lipid reactive oxygen species activity. Iron assay kit examined total iron content. Western blot tested the expression of ferroptosis- and TLR4/nuclear factor-kappaB (NF-κB)/NOD-like receptor 3 (NLRP3) pathway-associated proteins. Molecular docking predicted the binding affinity of emodin to TLR4. Emodin was noted to obstruct the migration, activation, inflammatory response, and ferroptosis of BV2 microglial cells induced by morphine. In addition, emodin had a high binding affinity with TLR4 and inactivated TLR4/NF-κB/NLRP3 pathway in morphine-challenged BV2 microglial cells. Upregulation of TLR4 partially countervailed the protective role of emodin against morphine-elicited BV2 microglial cell migration, activation, inflammation, and ferroptosis. Accordingly, emodin might target TLR4 and act as an inactivator of TLR4/NF-κB/NLRP3 pathway, thus inhibiting BV2 microglial activation and inflammation to mitigate morphine tolerance.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"48 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597687","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}
An imbalance of immune/inflammatory reactions aggravates secondary brain injury after traumatic brain injury (TBI) and can deteriorate clinical prognosis. So far, not enough therapeutic avenues have been found to prevent such an imbalance in the clinical setting. Progesterone has been shown to regulate immune/inflammatory reactions in many diseases and conveys a potential protective role in TBI. This study was designed to investigate the neuroprotective effects of progesterone associated with immune/inflammatory modulation in experimental TBI. A TBI model in adult male C57BL/6J mice was created using a controlled contusion instrument. After injury, the mice received consecutive progesterone therapy (8 mg/kg per day, i.p.) until euthanized. Neurological deficits were assessed via Morris water maze test. Brain edema was measured via the dry-wet weight method. Immunohistochemical staining and flow cytometry were used to examine the numbers of immune/inflammatory cells, including IBA-1 + microglia, myeloperoxidase + neutrophils, and regulatory T cells (Tregs). ELISA was used to detect the concentrations of IL-1β, TNF-α, IL-10, and TGF-β. Our data showed that progesterone therapy significantly improved neurological deficits and brain edema in experimental TBI, remarkably increased regulatory T cell numbers in the spleen, and dramatically reduced the activation and infiltration of inflammatory cells (microglia and neutrophils) in injured brain tissue. In addition, progesterone therapy decreased the expression of the pro-inflammatory cytokines IL-1β and TNF-α but increased the expression of the anti-inflammatory cytokine IL-10 after TBI. These findings suggest that progesterone administration could be used to regulate immune/inflammatory reactions and improve outcomes in TBI.
{"title":"Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury.","authors":"Ziwei Zhou, Yadan Li, Ruilong Peng, Mingming Shi, Weiwei Gao, Ping Lei, Jianning Zhang","doi":"10.1097/WNR.0000000000002013","DOIUrl":"10.1097/WNR.0000000000002013","url":null,"abstract":"<p><p>An imbalance of immune/inflammatory reactions aggravates secondary brain injury after traumatic brain injury (TBI) and can deteriorate clinical prognosis. So far, not enough therapeutic avenues have been found to prevent such an imbalance in the clinical setting. Progesterone has been shown to regulate immune/inflammatory reactions in many diseases and conveys a potential protective role in TBI. This study was designed to investigate the neuroprotective effects of progesterone associated with immune/inflammatory modulation in experimental TBI. A TBI model in adult male C57BL/6J mice was created using a controlled contusion instrument. After injury, the mice received consecutive progesterone therapy (8 mg/kg per day, i.p.) until euthanized. Neurological deficits were assessed via Morris water maze test. Brain edema was measured via the dry-wet weight method. Immunohistochemical staining and flow cytometry were used to examine the numbers of immune/inflammatory cells, including IBA-1 + microglia, myeloperoxidase + neutrophils, and regulatory T cells (Tregs). ELISA was used to detect the concentrations of IL-1β, TNF-α, IL-10, and TGF-β. Our data showed that progesterone therapy significantly improved neurological deficits and brain edema in experimental TBI, remarkably increased regulatory T cell numbers in the spleen, and dramatically reduced the activation and infiltration of inflammatory cells (microglia and neutrophils) in injured brain tissue. In addition, progesterone therapy decreased the expression of the pro-inflammatory cytokines IL-1β and TNF-α but increased the expression of the anti-inflammatory cytokine IL-10 after TBI. These findings suggest that progesterone administration could be used to regulate immune/inflammatory reactions and improve outcomes in TBI.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"352-360"},"PeriodicalIF":1.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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