Pub Date : 2024-01-01DOI: 10.2174/0115672026295640240212095049
Honggang Wu, Shu Chen, Guoliang You, Bo Lei, Li Chen, Jiachuan Wu, Niandong Zheng, Chao You
Background: Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke.
Objectives: This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH.
Methods: The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes.
Results: The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH.
Conclusion: AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.
背景:脑出血(ICH)是中风最常见的亚型之一:脑出血(ICH)是中风最常见的亚型之一:本研究旨在探讨黄芪皂苷 IV(AS-IV)对 ICH 后炎性损伤的作用机制:方法:通过注射胶原酶建立 ICH 模型,并用 ASIV(20 mg/kg 或 40 mg/kg)治疗。评估神经功能、双侧大脑半球和小脑的含水量以及脑组织的病理变化。酶联免疫吸附试验检测了白细胞介素-1β(IL-1β)、IL-18、肿瘤坏死因子-α、γ干扰素和IL-10的水平。反转录-定量聚合酶链反应和 Western 印迹法检测了 Kruppel 样因子 2(KLF2)、NOD 样受体家族含 pyrin 结构域 3(NLRP3)、GSDMD-N 和裂解-caspase-1 的水平。染色质免疫沉淀和双荧光素酶试验验证了 KLF2 和 NLRP3 之间的结合关系。在小鼠体内抑制 KLF2 或过表达 NLRP3,观察病理变化:结果:小鼠 ICH 后出现神经功能下降、含水量增加、严重病理损伤和炎症反应,脑组织中 NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 水平升高,KLF2 表达低下。经过AS-IV治疗后,神经功能障碍、脑含水量高、炎症反应和热蛋白沉积等症状得到缓解,而KLF2的表达却有所增加。KLF2 与 NLRP3 启动子区域结合并抑制其转录。KLF2的下调或NLRP3的上调逆转了AS-IV在抑制小鼠ICH后的脓毒症和减轻炎症损伤方面的作用:结论:AS-IV通过促进KLF2的表达抑制了NLRP3介导的脓毒症,减轻了ICH后小鼠的炎症损伤。
{"title":"The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage.","authors":"Honggang Wu, Shu Chen, Guoliang You, Bo Lei, Li Chen, Jiachuan Wu, Niandong Zheng, Chao You","doi":"10.2174/0115672026295640240212095049","DOIUrl":"10.2174/0115672026295640240212095049","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke.</p><p><strong>Objectives: </strong>This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH.</p><p><strong>Methods: </strong>The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes.</p><p><strong>Results: </strong>The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH.</p><p><strong>Conclusion: </strong>AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"74-85"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026289490240115075046
Nan-Nan Zhang, Zhi-Yong Wang, Jian-Min Chen, Zhi-Peng Yan, Guo-Xin Ni, Jun Ni
Background: Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values.
Methods: We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed.
Results: Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators.
Conclusion: According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aβ fiber neuropathy.
{"title":"Evaluation of Quantitative and Selective Sensory Fiber Dysfunction in Patients with Cirrhosis.","authors":"Nan-Nan Zhang, Zhi-Yong Wang, Jian-Min Chen, Zhi-Peng Yan, Guo-Xin Ni, Jun Ni","doi":"10.2174/0115672026289490240115075046","DOIUrl":"10.2174/0115672026289490240115075046","url":null,"abstract":"<p><strong>Background: </strong>Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values.</p><p><strong>Methods: </strong>We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed.</p><p><strong>Results: </strong>Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators.</p><p><strong>Conclusion: </strong>According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aβ fiber neuropathy.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"41-46"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Neurointervention via Transradial Access (TRA) is becoming increasingly popular as experience with this technique increases. However, approximately 8.6-10.3% of complex TRA cases are converted to femoral access due to a lack of support or radial artery spasm. This study aimed to assess the efficacy and safety of the TRUST (trans-radial coaxial catheter technique using a short sheath, Simmons catheter, and Tethys intermediate catheter) technique in interventional procedures via TRA.
Methods: This was a single-center retrospective analysis of 16 patients admitted to our institute between January 2023 to May 2023 to undergo endovascular interventions with the TRUST technique via the TRA.
Results: The mean age of the study population was 63.8 years, and 62.5% were male (10/16). The most common procedure was intracranial atherosclerotic stenosis (93.75%, 15/16). All procedures were performed successfully, and the most common procedures in our cohort were ballooning (50.0%, 8/16), stenting (18.75%, 3/16), and both procedures combined (31.25%, 1/16). All procedures were performed using the TRA, and the distal and proximal radial arteries were used for access in 31.35% (5/16) and 68.75% (11/16) of the cases, respectively. Technical success was achieved in all patients and most cases demonstrated mTICI ≥2b recanalization (93.75%, 15/16). In this case, no major access-site complications occurred.
Conclusion: The TRUST technique is technically safe and feasible and had a high technical success rate and low complication rate in our study. These results demonstrate that the TRUST technique is a promising alternative for patients undergoing complex neurointerventions.
{"title":"TRUST Technique for Neurointervention: A Promising Alternative for Complex Cases.","authors":"Xinzhao Jiang, Peng Wang, Fang Liu, Huadong Wu, Peng Jiang, Ruozhen Yuan, Sheng Zhang, Zongjie Shi","doi":"10.2174/0115672026291503240105093155","DOIUrl":"10.2174/0115672026291503240105093155","url":null,"abstract":"<p><strong>Background: </strong>Neurointervention via Transradial Access (TRA) is becoming increasingly popular as experience with this technique increases. However, approximately 8.6-10.3% of complex TRA cases are converted to femoral access due to a lack of support or radial artery spasm. This study aimed to assess the efficacy and safety of the TRUST (trans-radial coaxial catheter technique using a short sheath, Simmons catheter, and Tethys intermediate catheter) technique in interventional procedures via TRA.</p><p><strong>Methods: </strong>This was a single-center retrospective analysis of 16 patients admitted to our institute between January 2023 to May 2023 to undergo endovascular interventions with the TRUST technique via the TRA.</p><p><strong>Results: </strong>The mean age of the study population was 63.8 years, and 62.5% were male (10/16). The most common procedure was intracranial atherosclerotic stenosis (93.75%, 15/16). All procedures were performed successfully, and the most common procedures in our cohort were ballooning (50.0%, 8/16), stenting (18.75%, 3/16), and both procedures combined (31.25%, 1/16). All procedures were performed using the TRA, and the distal and proximal radial arteries were used for access in 31.35% (5/16) and 68.75% (11/16) of the cases, respectively. Technical success was achieved in all patients and most cases demonstrated mTICI ≥2b recanalization (93.75%, 15/16). In this case, no major access-site complications occurred.</p><p><strong>Conclusion: </strong>The TRUST technique is technically safe and feasible and had a high technical success rate and low complication rate in our study. These results demonstrate that the TRUST technique is a promising alternative for patients undergoing complex neurointerventions.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"47-53"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026303708240321035356
Wenxin Yuan, Lu An, Yunchao Wang, Ce Zong, Yinghao Yang, Hua Jin, Yuan Gao, Limei Wang, Yusheng Li, Yuming Xu, Yan Ji
Objective: Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV).
Methods: A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population.
Results: Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI.
Conclusion: Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.
{"title":"Analysis of the Relationship between Recent Small Subcortical Infarcts and Autonomic Nervous Dysfunction.","authors":"Wenxin Yuan, Lu An, Yunchao Wang, Ce Zong, Yinghao Yang, Hua Jin, Yuan Gao, Limei Wang, Yusheng Li, Yuming Xu, Yan Ji","doi":"10.2174/0115672026303708240321035356","DOIUrl":"10.2174/0115672026303708240321035356","url":null,"abstract":"<p><strong>Objective: </strong>Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV).</p><p><strong>Methods: </strong>A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population.</p><p><strong>Results: </strong>Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI.</p><p><strong>Conclusion: </strong>Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"166-176"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Cerebral Small Vessel Disease (CSVD) has not been systematically studied in patients with Transient Global Amnesia (TGA). We aimed to investigate the CSVD burden in patients with TGA and its relationship with TGA recurrence.
Methods: We retrospectively examined 69 patients diagnosed with TGA in a single center between January 2015 and November 2023. The overall CSVD burden and single CSVD imaging markers, including enlarged perivascular spaces in the hippocampus (H-EPVS), were measured in each patient and compared with those in 69 age- and sex-matched healthy controls. Multivariate logistic regression was performed to determine independent predictors of recurrence.
Results: Of the 69 included patients, 40 (58%) were female, and the median age was 67 years (range 42-83 years). Twenty-one patients (30.4%) showed dot-like hippocampal hyperintensities on diffusion-weighted imaging (DWI). The mean follow-up was 51 months. Sixteen patients (23.2%) experienced TGA recurrence. The burden of overall CSVD, lacunes, WMH, EPVS, and extensive H-EPVS was higher in TGA patients than in controls. TGA patients who experienced recurrence had a heavier overall CSVD burden, lower frequency of hippocampal DWI hyperintensities, and longer follow-up duration than those who had with single episode. In the multivariate analysis, only follow-up duration was an independent predictor of TGA recurrence.
Conclusion: The overall CSVD burden and extensive H-EPVS burden were higher in patients with TGA than healthy controls. Follow-up duration but not overall CSVD burden may predict TGA recurrence.
{"title":"Cerebral Small Vessel Disease Burden in Patients with Transient Global Amnesia and its Relationship with Recurrence.","authors":"Zhi-Li Wang, Simeng Wang, Dongtao Liu, Yuelei Lyu, Wei Qin, Wenli Hu","doi":"10.2174/0115672026309418240322060729","DOIUrl":"10.2174/0115672026309418240322060729","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral Small Vessel Disease (CSVD) has not been systematically studied in patients with Transient Global Amnesia (TGA). We aimed to investigate the CSVD burden in patients with TGA and its relationship with TGA recurrence.</p><p><strong>Methods: </strong>We retrospectively examined 69 patients diagnosed with TGA in a single center between January 2015 and November 2023. The overall CSVD burden and single CSVD imaging markers, including enlarged perivascular spaces in the hippocampus (H-EPVS), were measured in each patient and compared with those in 69 age- and sex-matched healthy controls. Multivariate logistic regression was performed to determine independent predictors of recurrence.</p><p><strong>Results: </strong>Of the 69 included patients, 40 (58%) were female, and the median age was 67 years (range 42-83 years). Twenty-one patients (30.4%) showed dot-like hippocampal hyperintensities on diffusion-weighted imaging (DWI). The mean follow-up was 51 months. Sixteen patients (23.2%) experienced TGA recurrence. The burden of overall CSVD, lacunes, WMH, EPVS, and extensive H-EPVS was higher in TGA patients than in controls. TGA patients who experienced recurrence had a heavier overall CSVD burden, lower frequency of hippocampal DWI hyperintensities, and longer follow-up duration than those who had with single episode. In the multivariate analysis, only follow-up duration was an independent predictor of TGA recurrence.</p><p><strong>Conclusion: </strong>The overall CSVD burden and extensive H-EPVS burden were higher in patients with TGA than healthy controls. Follow-up duration but not overall CSVD burden may predict TGA recurrence.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"234-242"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026305417240209062508
Yucheng Gu, Nihong Chen, Lin Zhu, Xiangliang Chen, Teng Jiang, Yingdong Zhang
Background: Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in Alzheimer's disease. However, despite recent investigations revealing various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss.
Objective: To investigate the potential pathogenesis-related molecular biological changes in the various stages of AD progression.
Methods: Whole transcriptome sequencing was performed on the peripheral blood of 7 normal cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between the NC group and each diseased group based on the differently expressed RNAs.
Results: In total, 3568 messenger RNAs (mRNAs), 142 miRNAs, 990 lncRNAs, and 183 circRNAs were identified as significantly differentially expressed across the four groups. GO and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified based on the differentially expressed RNAs between the NC group and the moD group.
Conclusion: The study suggests that circRNAs may be independent of mRNAs in AD pathogenesis and holds promise as potential biomarkers for AD clinical manifestations and pathological changes.
{"title":"Whole Transcriptome Sequencing of Peripheral Blood Identifies the Alzheimer's Disease-Related circRNA-miRNA-lncRNA Pathway.","authors":"Yucheng Gu, Nihong Chen, Lin Zhu, Xiangliang Chen, Teng Jiang, Yingdong Zhang","doi":"10.2174/0115672026305417240209062508","DOIUrl":"10.2174/0115672026305417240209062508","url":null,"abstract":"<p><strong>Background: </strong>Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in Alzheimer's disease. However, despite recent investigations revealing various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss.</p><p><strong>Objective: </strong>To investigate the potential pathogenesis-related molecular biological changes in the various stages of AD progression.</p><p><strong>Methods: </strong>Whole transcriptome sequencing was performed on the peripheral blood of 7 normal cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between the NC group and each diseased group based on the differently expressed RNAs.</p><p><strong>Results: </strong>In total, 3568 messenger RNAs (mRNAs), 142 miRNAs, 990 lncRNAs, and 183 circRNAs were identified as significantly differentially expressed across the four groups. GO and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified based on the differentially expressed RNAs between the NC group and the moD group.</p><p><strong>Conclusion: </strong>The study suggests that circRNAs may be independent of mRNAs in AD pathogenesis and holds promise as potential biomarkers for AD clinical manifestations and pathological changes.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"184-197"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background and aim: The impact of low platelet count on outcomes in patients with Acute Ischemic Stroke (AIS) undergoing Mechanical Thrombectomy (MT) is still unclear. In this study we have further explored the effect of thrombocytopenia on the safety and efficacy of MT in patients with anterior circulation Large Vessel Occlusion (LVO) stroke.
Materials and methods: Patients with AIS who underwent MT at our center between June 2015 and November 2021 were examined. Based on the platelet count recorded on admission patients were divided into two groups: those with thrombocytopenia (<150 × 109/L) and those without thrombocytopenia (≥ 150 × 109/L). Symptomatic Intracranial Hemorrhage (sICH) was the primary safety outcome. The efficacy outcome was functional independence defined as a 90-day modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression models were used to determine the risk factors for post-procedure sICH and 90-day functional outcomes.
Results: Among 302 patients included in the study, thrombocytopenia was detected in 111 (36.8%) cases. Univariate analysis showed age, the proportion of atrial fibrillation, the rates of sICH, 90-day poor outcomes, and mortality to be higher in patients with thrombocytopenia (all p <0.05). Multivariable analysis showed thrombocytopenia to be independently associated with a higher rate of sICH (OR 2.022, 95% CI 1.074-3.807, p =0.029) however, thrombocytopenia did not affect the 90-day functional outcomes (OR 1.045, 95%CI 0.490-2.230, p =0.909) and mortality (OR 1.389, 95% CI 0.467- 4.130 p = 0.554).
Conclusion: Thrombocytopenia may increase the risk of sICH but not affect the 90-day functional outcomes and mortality in patients with AIS treated with MT.
背景和目的:接受机械血栓切除术(MT)的急性缺血性卒中(AIS)患者中,血小板计数低对预后的影响尚不明确。在本研究中,我们进一步探讨了血小板减少对前循环大血管闭塞(LVO)卒中患者接受机械取栓术的安全性和有效性的影响:研究对象为2015年6月至2021年11月期间在本中心接受MT治疗的AIS患者。根据入院时记录的血小板计数,将患者分为两组:血小板减少组(结果:302 例患者中,有 1 例血小板减少,1 例血小板减少,1 例血小板减少,1 例血小板减少,1 例血小板减少在纳入研究的 302 例患者中,111 例(36.8%)发现血小板减少。单变量分析显示,血小板减少患者的年龄、心房颤动比例、sICH发生率、90天不良预后和死亡率均较高(均为p <;0.05)。多变量分析显示,血小板减少与较高的 sICH 发生率独立相关(OR 2.022,95% CI 1.074-3.807,p =0.029),但血小板减少并不影响 90 天功能预后(OR 1.045,95% CI 0.490-2.230,p =0.909)和死亡率(OR 1.389,95% CI 0.467-4.130 p =0.554):结论:血小板减少可能会增加接受 MT 治疗的 AIS 患者发生 sICH 的风险,但不会影响 90 天的功能预后和死亡率。
{"title":"Safety of Mechanical Thrombectomy for Acute Ischemic Stroke in Patients with Thrombocytopenia.","authors":"Sujie Zheng, Fang Liu, Liang Yu, Xinzhao Jiang, Xiaoyan Wen, Xu Wang, Zongjie Shi","doi":"10.2174/0115672026296867240626120014","DOIUrl":"10.2174/0115672026296867240626120014","url":null,"abstract":"<p><strong>Background and aim: </strong>The impact of low platelet count on outcomes in patients with Acute Ischemic Stroke (AIS) undergoing Mechanical Thrombectomy (MT) is still unclear. In this study we have further explored the effect of thrombocytopenia on the safety and efficacy of MT in patients with anterior circulation Large Vessel Occlusion (LVO) stroke.</p><p><strong>Materials and methods: </strong>Patients with AIS who underwent MT at our center between June 2015 and November 2021 were examined. Based on the platelet count recorded on admission patients were divided into two groups: those with thrombocytopenia (<150 × 10<sup>9</sup>/L) and those without thrombocytopenia (≥ 150 × 10<sup>9</sup>/L). Symptomatic Intracranial Hemorrhage (sICH) was the primary safety outcome. The efficacy outcome was functional independence defined as a 90-day modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression models were used to determine the risk factors for post-procedure sICH and 90-day functional outcomes.</p><p><strong>Results: </strong>Among 302 patients included in the study, thrombocytopenia was detected in 111 (36.8%) cases. Univariate analysis showed age, the proportion of atrial fibrillation, the rates of sICH, 90-day poor outcomes, and mortality to be higher in patients with thrombocytopenia (all p <0.05). Multivariable analysis showed thrombocytopenia to be independently associated with a higher rate of sICH (OR 2.022, 95% CI 1.074-3.807, p =0.029) however, thrombocytopenia did not affect the 90-day functional outcomes (OR 1.045, 95%CI 0.490-2.230, p =0.909) and mortality (OR 1.389, 95% CI 0.467- 4.130 p = 0.554).</p><p><strong>Conclusion: </strong>Thrombocytopenia may increase the risk of sICH but not affect the 90-day functional outcomes and mortality in patients with AIS treated with MT.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"286-291"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026299307240321090030
Shihang Luo, Rui Mao, Yi Li
Background: Recent research advancements have indicated a potential association between gut microbiota and cerebrovascular diseases, although the precise causative pathways and the directionality of this association remain to be fully elucidated.
Objective: This study utilized a bidirectional two-sample Mendelian Randomization (MR) methodology to explore the causal impact of gut microbiota compositions on the risk of cerebrovascular disease.
Methods: Genome-wide Association Study (GWAS) data pertaining to gut microbiota were obtained from the MiBioGen consortium. For Ischemic Stroke (IS), Transient Ischemic Attack (TIA), Vascular Dementia (VD), and Subarachnoid Hemorrhage (SAH), GWAS summary data were sourced from the FinnGen consortium, the IEU Open GWAS project, and the GWAS catalog, respectively.
Results: Our MR analyses identified that specific bacterial strains, notably those involved in the production of Short-chain Fatty Acids (SCFAs), including Barnesiella, Ruminococcus torques group, and Coprobacter, serve as protective factors against IS, TIA, and SAH. Linkage Disequilibrium Score Regression (LDSC) analysis corroborated a significant genetic correlation between these gut microbiota strains and various forms of cerebrovascular disease. In contrast, reverse MR analysis failed to establish a bidirectional causal relationship between genetically inferred gut microbiota profiles and these cerebrovascular conditions.
Conclusion: This investigation has pinpointed particular strains of gut microbiota that play protective or detrimental roles in cerebrovascular disease pathogenesis. These findings offer valuable insights that could be pivotal for the clinical management, prevention, and treatment of cerebrovascular diseases.
{"title":"Mendelian Randomization Highlights Gut Microbiota of Short-chain Fatty Acids' Producer as Protective Factor of Cerebrovascular Disease.","authors":"Shihang Luo, Rui Mao, Yi Li","doi":"10.2174/0115672026299307240321090030","DOIUrl":"10.2174/0115672026299307240321090030","url":null,"abstract":"<p><strong>Background: </strong>Recent research advancements have indicated a potential association between gut microbiota and cerebrovascular diseases, although the precise causative pathways and the directionality of this association remain to be fully elucidated.</p><p><strong>Objective: </strong>This study utilized a bidirectional two-sample Mendelian Randomization (MR) methodology to explore the causal impact of gut microbiota compositions on the risk of cerebrovascular disease.</p><p><strong>Methods: </strong>Genome-wide Association Study (GWAS) data pertaining to gut microbiota were obtained from the MiBioGen consortium. For Ischemic Stroke (IS), Transient Ischemic Attack (TIA), Vascular Dementia (VD), and Subarachnoid Hemorrhage (SAH), GWAS summary data were sourced from the FinnGen consortium, the IEU Open GWAS project, and the GWAS catalog, respectively.</p><p><strong>Results: </strong>Our MR analyses identified that specific bacterial strains, notably those involved in the production of Short-chain Fatty Acids (SCFAs), including Barnesiella, Ruminococcus torques group, and Coprobacter, serve as protective factors against IS, TIA, and SAH. Linkage Disequilibrium Score Regression (LDSC) analysis corroborated a significant genetic correlation between these gut microbiota strains and various forms of cerebrovascular disease. In contrast, reverse MR analysis failed to establish a bidirectional causal relationship between genetically inferred gut microbiota profiles and these cerebrovascular conditions.</p><p><strong>Conclusion: </strong>This investigation has pinpointed particular strains of gut microbiota that play protective or detrimental roles in cerebrovascular disease pathogenesis. These findings offer valuable insights that could be pivotal for the clinical management, prevention, and treatment of cerebrovascular diseases.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"32-40"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0115672026320884240620070951
Jianbin Sun, Tong Zhang, Chaoying Tang, Shuhang Fan, Qin Wang, Da Liu, Na Sai, Qi Ji, Weiwei Guo, Weiju Han
Background: Adherens junction in the blood-labyrinth barrier is largely unexplored because it is traditionally thought to be less important than the tight junction. Since increasing evidence indicates that it actually functions upstream of tight junction adherens junction may potentially be a better target for ameliorating the leakage of the blood-labyrinth barrier under pathological conditions such as acoustic trauma.
Aims: This study was conducted to investigate the pathogenesis of the disruption of adherens junction after acoustic trauma and explore potential therapeutic targets.
Methods: Critical targets that regulated the disruption of adherens junction were investigated by techniques such as immunofluorescence and Western blotting in C57BL/6J mice.
Results: Upregulation of Vascular Endothelial Growth Factor (VEGF) and downregulation of Pigment Epithelium-derived Factor (PEDF) coactivated VEGF-PEDF/VEGF receptor 2 (VEGFR2) signaling pathway in the stria vascularis after noise exposure. Downstream effector Src kinase was then activated to degrade VE-cadherin and dissociate adherens junction, which led to the leakage of the blood-labyrinth barrier. By inhibiting VEGFR2 or Src kinase, VE-cadherin degradation and blood-labyrinth barrier leakage could be attenuated, but Src kinase represented a better target to ameliorate blood-labyrinth barrier leakage as inhibiting it would not interfere with vascular endothelium repair, neurotrophy and pericytes proliferation mediated by upstream VEGFR2.
Conclusion: Src kinase may represent a promising target to relieve noise-induced disruption of adherens junction and hyperpermeability of the blood-labyrinth barrier.
背景:血-迷宫屏障中的粘连接头在很大程度上尚未被研究,因为传统上认为它不如紧密连接重要。越来越多的证据表明,粘连接头实际上在紧密连接的上游发挥作用,因此粘连接头有可能成为改善声外伤等病理情况下血流-迷宫屏障渗漏的更好靶点:方法:采用免疫荧光和 Western 印迹等技术对 C57BL/6J 小鼠进行了研究:结果:噪声暴露后,血管内皮生长因子(VEGF)的上调和色素上皮衍生因子(PEDF)的下调共同激活了血管纹中的VEGF-PEDF/VEGF受体2(VEGFR2)信号通路。下游效应因子 Src 激酶随后被激活,降解 VE-cadherin,解离粘连接头,从而导致血迷宫屏障渗漏。通过抑制血管内皮生长因子受体2或Src激酶,可减轻VE-adherin降解和血迷宫屏障渗漏,但Src激酶是改善血迷宫屏障渗漏的更好靶点,因为抑制它不会干扰由上游血管内皮生长因子受体2介导的血管内皮修复神经萎缩和周细胞增殖:结论:Src 激酶可能是缓解噪声引起的粘连接头破坏和血迷宫屏障高渗透性的一个有前途的靶点。
{"title":"Activation of Src Kinase Mediates the Disruption of Adherens Junction in the Blood-labyrinth Barrier after Acoustic Trauma.","authors":"Jianbin Sun, Tong Zhang, Chaoying Tang, Shuhang Fan, Qin Wang, Da Liu, Na Sai, Qi Ji, Weiwei Guo, Weiju Han","doi":"10.2174/0115672026320884240620070951","DOIUrl":"10.2174/0115672026320884240620070951","url":null,"abstract":"<p><strong>Background: </strong>Adherens junction in the blood-labyrinth barrier is largely unexplored because it is traditionally thought to be less important than the tight junction. Since increasing evidence indicates that it actually functions upstream of tight junction adherens junction may potentially be a better target for ameliorating the leakage of the blood-labyrinth barrier under pathological conditions such as acoustic trauma.</p><p><strong>Aims: </strong>This study was conducted to investigate the pathogenesis of the disruption of adherens junction after acoustic trauma and explore potential therapeutic targets.</p><p><strong>Methods: </strong>Critical targets that regulated the disruption of adherens junction were investigated by techniques such as immunofluorescence and Western blotting in C57BL/6J mice.</p><p><strong>Results: </strong>Upregulation of Vascular Endothelial Growth Factor (VEGF) and downregulation of Pigment Epithelium-derived Factor (PEDF) coactivated VEGF-PEDF/VEGF receptor 2 (VEGFR2) signaling pathway in the stria vascularis after noise exposure. Downstream effector Src kinase was then activated to degrade VE-cadherin and dissociate adherens junction, which led to the leakage of the blood-labyrinth barrier. By inhibiting VEGFR2 or Src kinase, VE-cadherin degradation and blood-labyrinth barrier leakage could be attenuated, but Src kinase represented a better target to ameliorate blood-labyrinth barrier leakage as inhibiting it would not interfere with vascular endothelium repair, neurotrophy and pericytes proliferation mediated by upstream VEGFR2.</p><p><strong>Conclusion: </strong>Src kinase may represent a promising target to relieve noise-induced disruption of adherens junction and hyperpermeability of the blood-labyrinth barrier.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"274-285"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567202621999240223164624
Kenneth Maiese
{"title":"Migraine Disorders, Neurovascular Disease, and the Underlying Role of Oxidative Stress.","authors":"Kenneth Maiese","doi":"10.2174/1567202621999240223164624","DOIUrl":"10.2174/1567202621999240223164624","url":null,"abstract":"","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"111-115"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}