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":null,"pages":null},"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}
Background: Obstructive sleep apnea (OSA) is one of the most common forms of sleep-disordered breathing. Studies have shown that certain changes in metabolism play an important role in the pathophysiology of OSA. However, the causal relationship between these metabolites and OSA remains unclear.
Aims: We use a mendelian randomization (MR) approach to investigate the causal associations between the genetic liability to metabolites and OSA.
Methods: We performed a 2-sample inverse-variance weighted mendelian randomization analysis to evaluate the causal effects of genetically determined 486 metabolites on OSA. Multiple sensitivity analyses were performed to assess pleiotropy. We used multivariate mendelian randomization analyses to assess confounding factors and mendelian randomization Bayesian model averaging to rank the significant biomarkers by their genetic evidence. We also conducted a metabolic pathway analysis to identify potential metabolic pathways.
Results: We identified 14 known serum metabolites (8 risk factors and 6 protective factors) and 12 unknown serum metabolites associated with OSA. These 14 known metabolites included 8 lipids( 1-arachidonoylglycerophosphoethanolamine, Tetradecanedioate, Epiandrosteronesulfate, Acetylca Glycerol3-phosphate, 3-dehydrocarnitine, Margarate17:0, Docosapentaenoaten3;22:5n3), 3 Aminoacids (Isovalerylcarnitine,3-methyl-2-oxobutyrate,Methionine), 2 Cofactors and vitamins [Bilirubin(E,ZorZ,E),X-11593--O-methylascorbate], 1Carbohydrate(1,6-anhydroglucose). We also identified several metabolic pathways that involved in the pathogenesis of OSA.
Conclusion: MR (mendelian randomization) approach was performed to identify 6 protective factors and 12 risk factors for OSA in the present study. 3-Dehydrocarnitine was the most significant risk factors for OSA. Our study also confirmed several significant metabolic pathways that were involved in the pathogenesis of OSA. Valine, leucine and isoleucine biosynthesis metabolic pathways were the most significant metabolic pathways that were involved in the pathogenesis of OSA.
{"title":"Causal Effects of Blood Metabolites and Obstructive Sleep Apnea: A Mendelian Randomization Study.","authors":"Jing-Hao Wu, Ying-Hao Yang, Yun-Chao Wang, Wen-Kai Yu, Shan-Shan Li, Yun-Yun Mei, Ce-Zong, Zi-Han Zhou, Hang-Hang Zhu, Liu-Chang He, Xin-Yu Li, Chang-He Shi, Yu-Sheng Li","doi":"10.2174/0115672026266627230921052416","DOIUrl":"10.2174/0115672026266627230921052416","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) is one of the most common forms of sleep-disordered breathing. Studies have shown that certain changes in metabolism play an important role in the pathophysiology of OSA. However, the causal relationship between these metabolites and OSA remains unclear.</p><p><strong>Aims: </strong>We use a mendelian randomization (MR) approach to investigate the causal associations between the genetic liability to metabolites and OSA.</p><p><strong>Methods: </strong>We performed a 2-sample inverse-variance weighted mendelian randomization analysis to evaluate the causal effects of genetically determined 486 metabolites on OSA. Multiple sensitivity analyses were performed to assess pleiotropy. We used multivariate mendelian randomization analyses to assess confounding factors and mendelian randomization Bayesian model averaging to rank the significant biomarkers by their genetic evidence. We also conducted a metabolic pathway analysis to identify potential metabolic pathways.</p><p><strong>Results: </strong>We identified 14 known serum metabolites (8 risk factors and 6 protective factors) and 12 unknown serum metabolites associated with OSA. These 14 known metabolites included 8 lipids( 1-arachidonoylglycerophosphoethanolamine, Tetradecanedioate, Epiandrosteronesulfate, Acetylca Glycerol3-phosphate, 3-dehydrocarnitine, Margarate17:0, Docosapentaenoaten3;22:5n3), 3 Aminoacids (Isovalerylcarnitine,3-methyl-2-oxobutyrate,Methionine), 2 Cofactors and vitamins [Bilirubin(E,ZorZ,E),X-11593--O-methylascorbate], 1Carbohydrate(1,6-anhydroglucose). We also identified several metabolic pathways that involved in the pathogenesis of OSA.</p><p><strong>Conclusion: </strong>MR (mendelian randomization) approach was performed to identify 6 protective factors and 12 risk factors for OSA in the present study. 3-Dehydrocarnitine was the most significant risk factors for OSA. Our study also confirmed several significant metabolic pathways that were involved in the pathogenesis of OSA. Valine, leucine and isoleucine biosynthesis metabolic pathways were the most significant metabolic pathways that were involved in the pathogenesis of OSA.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159529","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: 10.2174/0115672026283323240108052711
Yutong Hou, Wei Qin, Shuna Yang, Yue Li, Lei Yang, Wenli Hu
Objective: Diffusion-weighted imaging (DWI) is commonly detected after spontaneous intracerebral hemorrhage (sICH) and is associated with poor functional outcomes. However, the etiology and significance of DWI lesions remain unclear. Thus, our study aimed to explore the prevalence and risk factors of acute ischemic lesions in sICH and discussed the possible mechanisms.
Methods: We conducted a retrospective review of a consecutive cohort of 408 patients from June 2013 to October 2019 with sICH, who had brain computed tomography (CT) and magnetic resonance imaging (MRI) within 14 days of symptoms onset. Acute ischemic lesions were assessed on MRI using DWI lesions. We compared the clinical and imaging characteristics of patients with and without DWI lesions. The data were analyzed by univariate and multivariate logistic regression.
Results: Among the enrolled 408 patients, the mean age was 56.8 ± 14.5 years, 68 (16.7%) of them had been diagnosed with diabetes mellitus (DM). DWI lesions were observed in 89 (21.8%) patients, and most of them had a history of lacunar infarctions, which were located in cortical or subcortical. In multivariate logistic regression analysis, DM (odds ratio (OR) 3.962, p <0.001), severe deep white matter hypertensities (DWMH) (OR 2.463, p =0.001) and severe centrum semiovale enlarged perivascular spaces (CSO-EPVS) (OR 2.679, p =0.001) were independently associated with the presence of DWI lesions.
Conclusion: In our cohort, we found DM, severe DWMH and severe CSO-EPVS were the independent risk factors in sICH patients with DWI lesions.
{"title":"Diffusion-weighted Imaging Detection of Acute Ischemia Brain Lesions in Spontaneous Intracerebral Hemorrhage Associated with White Matter Hyperintensities, Enlarged Perivascular Spaces and Diabetes Mellitus.","authors":"Yutong Hou, Wei Qin, Shuna Yang, Yue Li, Lei Yang, Wenli Hu","doi":"10.2174/0115672026283323240108052711","DOIUrl":"10.2174/0115672026283323240108052711","url":null,"abstract":"<p><strong>Objective: </strong>Diffusion-weighted imaging (DWI) is commonly detected after spontaneous intracerebral hemorrhage (sICH) and is associated with poor functional outcomes. However, the etiology and significance of DWI lesions remain unclear. Thus, our study aimed to explore the prevalence and risk factors of acute ischemic lesions in sICH and discussed the possible mechanisms.</p><p><strong>Methods: </strong>We conducted a retrospective review of a consecutive cohort of 408 patients from June 2013 to October 2019 with sICH, who had brain computed tomography (CT) and magnetic resonance imaging (MRI) within 14 days of symptoms onset. Acute ischemic lesions were assessed on MRI using DWI lesions. We compared the clinical and imaging characteristics of patients with and without DWI lesions. The data were analyzed by univariate and multivariate logistic regression.</p><p><strong>Results: </strong>Among the enrolled 408 patients, the mean age was 56.8 ± 14.5 years, 68 (16.7%) of them had been diagnosed with diabetes mellitus (DM). DWI lesions were observed in 89 (21.8%) patients, and most of them had a history of lacunar infarctions, which were located in cortical or subcortical. In multivariate logistic regression analysis, DM (odds ratio (OR) 3.962, p <0.001), severe deep white matter hypertensities (DWMH) (OR 2.463, p =0.001) and severe centrum semiovale enlarged perivascular spaces (CSO-EPVS) (OR 2.679, p =0.001) were independently associated with the presence of DWI lesions.</p><p><strong>Conclusion: </strong>In our cohort, we found DM, severe DWMH and severe CSO-EPVS were the independent risk factors in sICH patients with DWI lesions.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577284","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: 10.2174/0115672026299546240130092550
Zhengrong Wu, Ke Zhang, Ce Zong, Hongbing Liu, Yanhong Wang, Yuming Xu, Yuan Gao
Background: Research has linked enlarged perivascular spaces (EPVS) to cerebral venous reflux (CVR) in patients with hypertensive intracerebral hemorrhage, but it is unclear whether this association exists in recent small subcortical infarct (RSSI) patients.
Objective: This study aimed to investigate the correlation between EPVS and CVR in patients with RSSI.
Method: This study included 297 patients, selected from patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University. CVR was assessed by time-of-flight magnetic resonance angiography (TOF-MRA). The relationship between EPVS and CVR was studied using multiple logistic regression analysis.
Results: This study included patients with an average age of 59.84±12.27 years, including 201 males (67.7%). CVR was observed in 40 (13.5%) patients. Compared to the group without CVR, the proportions of male patients and patients with a history of smoking and drinking were higher in the CVR group. The proportions of high-grade EPVS in the centrum semiovale region [23 cases (57.5%) vs. 108 cases (42.0%), p =0.067] and the basal ganglia region [30 cases (75.0%) vs. 133 cases (51.8%), p =0.006] were higher in the CVR group. After multiple logistic regression analysis, high-grade EPVS in the basal ganglia region was still associated with CVR (OR, 2.68; 95% CI, 1.22-5.87;p=0.014).
Conclusion: In the population with RSSI, EPVS in basal ganglia is significantly associated with CVR, suggesting a close relationship between venous dysfunction and the formation of EPVS.
{"title":"Enlarged Perivascular Space in the Basal Ganglia is Associated with Cerebral Venous Reflux in Patients with Recent Small Subcortical Infarction.","authors":"Zhengrong Wu, Ke Zhang, Ce Zong, Hongbing Liu, Yanhong Wang, Yuming Xu, Yuan Gao","doi":"10.2174/0115672026299546240130092550","DOIUrl":"10.2174/0115672026299546240130092550","url":null,"abstract":"<p><strong>Background: </strong>Research has linked enlarged perivascular spaces (EPVS) to cerebral venous reflux (CVR) in patients with hypertensive intracerebral hemorrhage, but it is unclear whether this association exists in recent small subcortical infarct (RSSI) patients.</p><p><strong>Objective: </strong>This study aimed to investigate the correlation between EPVS and CVR in patients with RSSI.</p><p><strong>Method: </strong>This study included 297 patients, selected from patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University. CVR was assessed by time-of-flight magnetic resonance angiography (TOF-MRA). The relationship between EPVS and CVR was studied using multiple logistic regression analysis.</p><p><strong>Results: </strong>This study included patients with an average age of 59.84±12.27 years, including 201 males (67.7%). CVR was observed in 40 (13.5%) patients. Compared to the group without CVR, the proportions of male patients and patients with a history of smoking and drinking were higher in the CVR group. The proportions of high-grade EPVS in the centrum semiovale region [23 cases (57.5%) vs. 108 cases (42.0%), <i>p</i> =0.067] and the basal ganglia region [30 cases (75.0%) vs. 133 cases (51.8%), <i>p</i> =0.006] were higher in the CVR group. After multiple logistic regression analysis, high-grade EPVS in the basal ganglia region was still associated with CVR (OR, 2.68; 95% CI, 1.22-5.87;<i>p</i>=0.014).</p><p><strong>Conclusion: </strong>In the population with RSSI, EPVS in basal ganglia is significantly associated with CVR, suggesting a close relationship between venous dysfunction and the formation of EPVS.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699121","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: 10.2174/1567202620999231027155308
Kenneth Maiese
{"title":"Microglia: Formidable Players in Alzheimer's Disease and Other Neurodegenerative Disorders.","authors":"Kenneth Maiese","doi":"10.2174/1567202620999231027155308","DOIUrl":"10.2174/1567202620999231027155308","url":null,"abstract":"","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232865","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: 10.2174/0115672026298727240219110134
Yongho Kwon, Ho Jun Yi, Dong-Seong Shin, Bum-Tae Kim
Objective: Emboli commonly occurs in mechanical thrombectomy (MT). The objective of this study was to analyze predicting factors of emboli after MT.
Methods: Patients who underwent MT with successful reperfusion for anterior circulation occlusion were enrolled. Emboli included distal emboli at digital subtraction angiography (DSA) and unexpected embolic infarct on diffusion-weighted image (DWI) without distal emboli at DSA. Baseline characteristics, procedural details, angiographic outcomes, and clinical outcomes were reviewed. Multivariable analyses were performed to evaluate predictive factors for the occurrence of emboli.
Results: Of 601 patients, 149 (24.8%) patients had distal emboli at DSA, and 169 (28.1%) patients had unexpected embolic infarction on DWI even without distal emboli at DSA. A total of 318 (52.9%) patients were enrolled in the embolic group, and 283 (47.1%) patients were assigned to the non-embolic group. In multivariate analysis, larger microcatheter (OR 1.26, 95% CI 1.12-1.94; p = 0.047), clot passage (OR 1.33, 95% CI 1.07-1.87; p = 0.041), use of balloon guide catheter (BGC) (OR 0.70, 95% CI 0.52-0.92; p = 0.014), early ballooning of BGC (OR 0.68, 95% CI 0.50-0.90; p = 0.009), and longer stent retriever (OR 0.72, 95% CI 0.54-0.90; p = 0.029) were associated with occurrence of emboli.
Conclusion: MT with only a stent retriever, use of a larger microcatheter, and clot passage might increase the risk of emboli. In contrast, contact aspiration thrombectomy, use of BGC, early ballooning of BGC, and use of longer stent retrievers could reduce the chance of emboli.
{"title":"Predictors of Emboli in Mechanical Thrombectomy for Anterior Circulation Stroke.","authors":"Yongho Kwon, Ho Jun Yi, Dong-Seong Shin, Bum-Tae Kim","doi":"10.2174/0115672026298727240219110134","DOIUrl":"10.2174/0115672026298727240219110134","url":null,"abstract":"<p><strong>Objective: </strong>Emboli commonly occurs in mechanical thrombectomy (MT). The objective of this study was to analyze predicting factors of emboli after MT.</p><p><strong>Methods: </strong>Patients who underwent MT with successful reperfusion for anterior circulation occlusion were enrolled. Emboli included distal emboli at digital subtraction angiography (DSA) and unexpected embolic infarct on diffusion-weighted image (DWI) without distal emboli at DSA. Baseline characteristics, procedural details, angiographic outcomes, and clinical outcomes were reviewed. Multivariable analyses were performed to evaluate predictive factors for the occurrence of emboli.</p><p><strong>Results: </strong>Of 601 patients, 149 (24.8%) patients had distal emboli at DSA, and 169 (28.1%) patients had unexpected embolic infarction on DWI even without distal emboli at DSA. A total of 318 (52.9%) patients were enrolled in the embolic group, and 283 (47.1%) patients were assigned to the non-embolic group. In multivariate analysis, larger microcatheter (OR 1.26, 95% CI 1.12-1.94; <i>p</i> = 0.047), clot passage (OR 1.33, 95% CI 1.07-1.87; <i>p</i> = 0.041), use of balloon guide catheter (BGC) (OR 0.70, 95% CI 0.52-0.92; <i>p</i> = 0.014), early ballooning of BGC (OR 0.68, 95% CI 0.50-0.90; <i>p</i> = 0.009), and longer stent retriever (OR 0.72, 95% CI 0.54-0.90; <i>p</i> = 0.029) were associated with occurrence of emboli.</p><p><strong>Conclusion: </strong>MT with only a stent retriever, use of a larger microcatheter, and clot passage might increase the risk of emboli. In contrast, contact aspiration thrombectomy, use of BGC, early ballooning of BGC, and use of longer stent retrievers could reduce the chance of emboli.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029798","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}
Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated.
Methods: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment.
Results: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation.
Conclusion: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.
{"title":"Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.","authors":"Han-Rui Zhang, Gu-Quan Ma, He-Qun Lv, Yao-Ting Feng, Yong-Jun Peng","doi":"10.2174/0115672026294183240207115956","DOIUrl":"10.2174/0115672026294183240207115956","url":null,"abstract":"<p><p>Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated.</p><p><strong>Methods: </strong>All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on \"Renzhong\" (DU26) and \"Baihui\" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment.</p><p><strong>Results: </strong>EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation.</p><p><strong>Conclusion: </strong>The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975074","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: Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes.
Objective: We aimed to study the incidence, risk factors and prognosis of END after BT.
Methods: From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors.
Results: The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001).
Conclusion: It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.
{"title":"Risk Factors and Prognosis of Early Neurological Deterioration after Bridging Therapy.","authors":"Yiju Xie, Shengyu Li, Liuyu Liu, Shiting Tang, Yayuan Liu, Shuangquan Tan, Zhijian Liang","doi":"10.2174/0115672026287986240104074006","DOIUrl":"10.2174/0115672026287986240104074006","url":null,"abstract":"<p><strong>Background: </strong>Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes.</p><p><strong>Objective: </strong>We aimed to study the incidence, risk factors and prognosis of END after BT.</p><p><strong>Methods: </strong>From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors.</p><p><strong>Results: </strong>The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001).</p><p><strong>Conclusion: </strong>It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682161","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: 10.2174/0115672026304601240307051654
Gustavo da Fontoura Galvão, Ricardo Castro Filho, Alexandre Alexandre Martins Cunha, Andre Guimarães Soares, Marcos Antônio Dellaretti Filho, Jorge Marcondes de Souza
Background: Cerebral Cavernous Malformation (CCM) is one of the most common types of vascular malformation of the central nervous system. Intracerebral hemorrhage, seizures, and lesional growth are the main clinical manifestations. Natural history studies have tried to identify many risk factors; however, the clinical course remains highly unpredictable.
Objective: Here, we have analyzed a multicenter CCM cohort looking for the differential clinical data regarding the patients harboring supra and/or infratentorial cavernous malformations in order to better understand risk factors involved in the anatomical location of the unique neurosurgical disease.
Methods: We have presented a multicenter, Propensity Score Matched (PSM), case-control study including 149 consecutive CCM cases clinically evaluated from May 2017 to December 2022 from three different neurosurgical centers. Epidemiological data were defined at each clinical assessment. Logistic regression was used to identify the independent contribution of each possible risk factor to the bleeding risk. To balance baseline covariates between patients with and without symptoms, and specifically between those with and without symptomatic bleeding, we used a PSM strategy. The Kaplan-Meier curve was drawn to evaluate if patients with infratentorial lesions had a greater chance of bleeding earlier in their life.
Results: The presence of infratentorial lesions was a risk factor in the multivariate analysis comparing the bleeding risk with pure asymptomatic individuals (OR: 3.23, 95% CI 1.43 - 7.26, P = 0.005). Also, having an infratentorial CCM was a risk factor after PSM (OR: 4.56, 95% CI 1.47 - 14.10, P = 0.008). The presence of an infratentorial lesion was related to precocity of symptoms when the time to first bleed was compared to all other clinical presentations in the overall cohort (P = 0.0328) and in the PSM group (P = 0.03).
Conclusion: Here, we have provided some evidence that infratentorial cerebral cavernous malformation may have a more aggressive clinical course, being a risk factor for symptomatic haemorrhage and precocity of bleeding.
{"title":"Infratentorial Cerebral Cavernous Malformation May be a Risk Factor for Symptomatic Bleeding and Precocity of Symptoms: A Multicenter, Propensity Score Matched, Case-Control Study.","authors":"Gustavo da Fontoura Galvão, Ricardo Castro Filho, Alexandre Alexandre Martins Cunha, Andre Guimarães Soares, Marcos Antônio Dellaretti Filho, Jorge Marcondes de Souza","doi":"10.2174/0115672026304601240307051654","DOIUrl":"10.2174/0115672026304601240307051654","url":null,"abstract":"<p><strong>Background: </strong>Cerebral Cavernous Malformation (CCM) is one of the most common types of vascular malformation of the central nervous system. Intracerebral hemorrhage, seizures, and lesional growth are the main clinical manifestations. Natural history studies have tried to identify many risk factors; however, the clinical course remains highly unpredictable.</p><p><strong>Objective: </strong>Here, we have analyzed a multicenter CCM cohort looking for the differential clinical data regarding the patients harboring supra and/or infratentorial cavernous malformations in order to better understand risk factors involved in the anatomical location of the unique neurosurgical disease.</p><p><strong>Methods: </strong>We have presented a multicenter, Propensity Score Matched (PSM), case-control study including 149 consecutive CCM cases clinically evaluated from May 2017 to December 2022 from three different neurosurgical centers. Epidemiological data were defined at each clinical assessment. Logistic regression was used to identify the independent contribution of each possible risk factor to the bleeding risk. To balance baseline covariates between patients with and without symptoms, and specifically between those with and without symptomatic bleeding, we used a PSM strategy. The Kaplan-Meier curve was drawn to evaluate if patients with infratentorial lesions had a greater chance of bleeding earlier in their life.</p><p><strong>Results: </strong>The presence of infratentorial lesions was a risk factor in the multivariate analysis comparing the bleeding risk with pure asymptomatic individuals (OR: 3.23, 95% CI 1.43 - 7.26, P = 0.005). Also, having an infratentorial CCM was a risk factor after PSM (OR: 4.56, 95% CI 1.47 - 14.10, P = 0.008). The presence of an infratentorial lesion was related to precocity of symptoms when the time to first bleed was compared to all other clinical presentations in the overall cohort (P = 0.0328) and in the PSM group (P = 0.03).</p><p><strong>Conclusion: </strong>Here, we have provided some evidence that infratentorial cerebral cavernous malformation may have a more aggressive clinical course, being a risk factor for symptomatic haemorrhage and precocity of bleeding.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121653","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: 10.2174/0115672026290996240307072539
Jing-Xuan Li, Dai Shi, Si-Ying Ren, Guo-Feng Wu
Background: Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABAA.
Objective: This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE.
Methods: The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABAA receptor α1, β2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR.
Results: The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABAA receptors α1, β2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy.
Conclusion: Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABAA receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.
背景:耐药性癫痫(DRE)是一种难治性神经系统疾病。大量证据表明,γ-氨基丁酸-a(GABAA)受体可能是导致癫痫耐药性产生的机制之一。人们还知道,cAMP 反应元件结合蛋白(CREB)在 GABAA 的转录调控中可能起着关键作用:本研究探讨了 CREB 在 DRE 发病中的作用,以及 CREB 对 DRE 中 GABA 相关受体的影响:方法:通过慢病毒转染增加或减少正常大鼠海马中CREB的表达,然后对其进行锂-匹罗卡品诱导的癫痫模型试验。苯巴比妥钠(PB)和卡马西平(CBZ)用于选择耐药癫痫模型。通过Western印迹和荧光定量PCR检测大鼠海马中GABAA受体α1、β2和γ2亚基以及CREB蛋白的表达水平:结果:与对照组相比,过表达组大鼠癫痫发作的频率和持续时间增加。此外,表达减少组的癫痫发作严重程度、频率和持续时间均有所下降。对海马CREB蛋白和CREB mRNA表达水平的分析也得出了类似的结果。改变大鼠海马中CREB蛋白的表达可负向调节GABAA受体α1、β2和γ2的表达和转录水平,这表明CREB可能是开发癫痫治疗方案和药物的潜在靶点:我们的研究表明,CREB表达的增强会促进DRE的发生,并负向调节GABAA受体水平,抑制CREB的表达可降低DRE的发病率。
{"title":"Increased Cyclic Adenosine Monophosphate Responsive Element is Closely Associated with the Pathogenesis of Drug-resistant Epilepsy.","authors":"Jing-Xuan Li, Dai Shi, Si-Ying Ren, Guo-Feng Wu","doi":"10.2174/0115672026290996240307072539","DOIUrl":"10.2174/0115672026290996240307072539","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABA<sub>A</sub>.</p><p><strong>Objective: </strong>This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE.</p><p><strong>Methods: </strong>The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABA<sub>A</sub> receptor α1, β2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR.</p><p><strong>Results: </strong>The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABA<sub>A</sub> receptors α1, β2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy.</p><p><strong>Conclusion: </strong>Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABA<sub>A</sub> receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103017","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}