Current neurovascular research最新文献

Background: High brain-derived neurotrophic factor (BDNF) concentrations have been found to be associated with a decreased risk of Alzheimer's disease (AD) in observational studies, but the causality for this association remains unclear. Therefore, we aimed to examine the association between genetically determined plasma BDNF levels and AD using a two-sample Mendelian randomization (MR) method.

Methods: Twenty single-nucleotide polymorphisms associated with plasma BDNF concentrations were identified as genetic instruments based on a genome-wide association study with 3301 European individuals. Summary-level data on AD were obtained from the International Genomics of Alzheimer's Project, involving 21,982 AD cases and 41,944 controls of European ancestry. To evaluate the relationship between plasma BDNF concentrations and AD, we employed the inverse-variance weighted method along with a series of sensitivity analyses.

Results: The inverse-variance weighted MR analysis showed that genetically determined BDNF concentrations were associated with a decreased risk of AD (odds ratio per SD increase, 0.91; 95% confidence interval, 0.86-0.96; p =0.001). The association between plasma BDNF concentrations and AD was further confirmed through sensitivity analyses using different MR methods, and MR-Egger regression suggested no directional pleiotropy for this association.

Conclusion: Genetically determined BDNF levels were associated with a decreased risk of AD, suggesting that BDNF was implicated in the development of AD and might be a promising target for the prevention of AD.

Objectives: To investigate the correlation between evening melatonin timing secretion, dim light melatonin onset (DLMO), and post-stroke depression (PSD) in acute ischemic stroke patients and their influence on the improvement of depressive symptoms.

Materials and methods: 120 patients with a recent magnetic resonance imaging confirmed stroke were included. Salivary melatonin samples were collected at 5 time points within 1 week after hospitalization (7 p.m.-11 p.m., 1 sample per hour). The circadian phase was defined by calculating DLMO secretion. Post-stroke depressive symptoms were evaluated by the 17-item Hamilton Rating Scale for Depression (HRSD) both on day 7 of hospitalization and 3 months after stroke. Patients were divided into PSD and non-PSD groups based on whether the acute phase HRSD score was ≥8. Similarly, patients were divided into the improved depressive symptoms (IDS) and no improvement in depressive symptoms (non-IDS) groups based on whether the HRSD score at 3 months was lower than at baseline. Neurological recovery at 3 months was assessed using the modified Rankin Scale (mRS).

Results: The difference in DLMO between PSD and non-PSD patients was not statistically significant (p =0.173). In the non-IDS group, there was a significant decrease in melatonin secretion at 10 p.m. (p =0.012), and DLMO was significantly later than in the IDS group (p =0.017). Logistic regression analysis showed that DLMO (OR 1.91, 95%CI:1.13-3.23, p = 0.016) was an independent risk factor for persistent no improvement in depressive symptoms, which was associated with a markedly worse prognosis (p <.001).

Conclusion: Our findings suggest possible interventions for the very early identification of non-IDS patients.

Background: The annualized recurrent stroke rate in patients with Embolic Stroke of Undetermined Source (ESUS) under antiplatelet therapy is around 4.5%. Only a fraction of these patients will develop atrial fibrillation (FA), to which a stroke can be attributed retrospectively. The challenge is to identify patients at risk of occult AF during follow-up.

Objective: This work aims to determine clinical factors and electrocardiographic and ultrasound parameters that can predict occult AF in patients with ESUS and build a simple predictive score applicable worldwide.

Methods: This is a single-center, registry-based retrospective study conducted at the stroke unit of Sahloul University Hospital, Sousse, Tunisia, between January 2016 and December 2020. Consecutive patients meeting ESUS criteria were monitored for a minimum of one year, with a standardized follow-up consisting of outpatient visits, including ECG every three months and a new 24-hour Holter monitoring in case of palpitations. We performed multivariate stepwise regression to identify predictors of new paroxysmal AF among initial clinical, electrocardiographic (ECG and 24-hour Holter monitoring) and echocardiographic parameters. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integerbased point-scoring system.

Results: Three hundred patients met the criteria for ESUS. Among them, 42 (14%) patients showed at least one episode of paroxysmal AF during a median follow-up of two years. In univariate analysis, age, gender, coronary artery disease, history of ischemic stroke, higher NIHSS at admission and lower NIHSS at discharge, abnormal P-wave axis, prolonged P-wave duration, premature atrial contractions (PAC) frequency of more than 500/24 hours, and left atrial (LA) mean area of more than 20 cm² were associated with the risk of occurrence of paroxysmal AF. We proposed an AF predictive score based on (1.771 x NIHSS score at admission) + (10.015 x P-wave dispersion; coded 1 if yes and 0 if no) + (9.841x PAC class; coded 1 if ≥500 and 0 if no) + (9.828x LA class surface; coded 1 if ≥20 and 0 if no) + (0.548xNIHSS score at discharge) + 0.004. A score of ≥33 had a sensitivity of 76% and a specificity of 93%.

Conclusion: In this cohort of patients with ESUS, NIHSS at both admission and discharge, Pwave dispersion, PAC≥500/24h on a 24-hour Holter monitoring, and LA surface area≥20 cm² provide a simple AF predictive score with very reasonable sensitivity and specificity and is applicable almost worldwide. An external validation of this score is ongoing.

Background: Major depression has a complex and multifactorial etiology constituted by the interaction between genetic and environmental factors in its development.

Objective: The aim of this study was to evaluate the effects of sodium butyrate (SD) on epigenetic enzyme alterations in rats subjected to animal models of depression induced by maternal deprivation (MD) or chronic mild stress (CMS).

Methods: To induce MD, male Wistar rats were deprived of maternal care during the first 10 days of life. To induce CMS, rats were subjected to the CMS for 40 days. Adult rats were then treated with daily injections of SD for 7 days. Animals were subjected to the forced swimming test (FST), and then, histone deacetylase (HDAC), histone acetyltransferase (HAT), and DNA methyltransferase (DNMT) activities were evaluated in the brain.

Results: MD and CMS increased immobility time in FST and increased HDAC and DNMT activity in the animal brains. SD reversed increased immobility induced by both animal models and the alterations in HDAC and DNMT activities. There was a positive correlation between enzyme activities and immobility time for both models. HDAC and DNMT activities also presented a positive correlation between themselves.

Conclusion: These results suggest that epigenetics can play an important role in major depression pathophysiology triggered by early or late life stress and its treatment.

Background: Pneumonia causes significant morbidity and mortality and has been associated with cardiovascular complications. Our study aimed to investigate the incidence of ischemic and hemorrhagic strokes following bacterial pneumonia.

Methods: Between 1997 and 2012, 10,931 subjects with bacterial pneumonia and 109,310 controls were enrolled from the Taiwan National Health Insurance Research Database, and were followed up to the end of 2013. The risk of stroke was estimated in Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: When compared to the control group, subjects in the bacterial pneumonia group had a higher incidence of developing ischemic stroke (2.7% versus 0.4%, p <0.001) and hemorrhagic stroke (0.7% versus 0.1%, p <0.001). The risk of stroke increases with repeated hospitalizations due to bacterial pneumonia. Across bacterial etiologies, bacterial pneumonia was a significant risk factor among 775 subjects who developed ischemic stroke (HR, 5.72; 95% CI, 4.92-6.65) and 193 subjects who developed hemorrhagic stroke (HR, 5.33; 95% CI, 3.91-7.26).

Conclusion: The risks of developing ischemic stroke and hemorrhagic stroke are significant following bacterial pneumonia infection. The risk factors, clinical outcomes, and the disease course should also be profiled to better inform the monitoring of stroke development and the clinical management of bacterial pneumonia patients.

Background: Cerebral hyperperfusion syndrome (CHS) is known as a complication after bypass surgery for Moyamoya disease (MMD). However, the incidence of CHS has not been accurately reported, and there is no consensus on the risk factors associated with it.

Aim: The aim of this study was to determine the risk factors associated with postoperative CHS after surgical combined revascularization used to treat adult patients with MMD.

Objective: To assess the frequency and characteristics of CHS in patients with MMD after revascularization operations.

Methods: Patients who received combined revascularization from Jan 2021 to Nov 2022 were retrospectively reviewed. Preoperative clinical characteristics and radiographic features were recorded. Postoperative CHS after surgery were examined. Multivariate logistic regression analyses were performed to identify the risk factors for CHS.

Results: A total of 133 patients (141 hemispheres) were included in this study. Postoperative CHS were observed in 28 hemispheres (19.8%), including focal cerebral hyperperfusion syndrome (FCHS) in 20 hemispheres (14.2%), hemorrhage in 4 (2.8%) hemispheres, seizures in 4 (2.8%) hemispheres. The results of multivariate logistic regression analysis indicated that preoperative hypertension (OR 4.705, 95% CI 1.323 ~ 12.554, p = 0.014), cerebral hemorrhage onset (OR 5.390, 95% CI 1.408 ~ 20.642, p = 0.014) and higher Hct level (OR 1.171, 95% CI 1.051 ~ 1.305, p = 0.004) were significantly associated with CHS after combined revascularization.

Conclusions: Preoperative hypertension, cerebral hemorrhage onset, and higher Hct level were independent risk factors for CHS after combined revascularization.

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.

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.

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.

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.