Current neurovascular research最新文献

Background and purpose: Several pieces of evidence suggest that serum lactate hydrogenase (LDH) level is associated with the pathological process of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). This research aimed to investigate the associations of serum LDH level with the occurrence of DCI in aSAH patients.

Methods: A total of 122 patients diagnosed with aSAH within 72h of onset were retrospectively enrolled. The serum levels of LDH between 7:00-8:00 am on day 1, day 3 and day 7, patients' demographics, and clinical features were collected. Computed tomography perfusion was performed within 7 days after aSAH. The occurrence of DCI was recorded during the hospitalization.

Results: Among all the enrolled patients, 43 (35.2%) developed DCI during hospitalization. Patients occurred DCI were always accompanied by more serious clinical features and found with higher serum LDH levels. LDH levels on day 3 and day 7 after onset were independently associated with the occurrence of DCI and showed high predictive value according to the receiver operating characteristic (ROC) curve. Moreover, there was a strong correlation between LDH and mean cerebral blood flow, transit time, and mean time to peak.

Conclusion: Serum LDH level on day 3 and day 7 may be a valuable, convenient, and rapid predictive indicator for the occurrence of DCI in aSAH patients.

Objectives: To assess the association between carotid artery plaques and the risk of incident intracerebral hemorrhage (ICH) event in high-risk individuals for stroke.

Methods: We conducted a population-based cohort study using the longitudinal participant-level data of a multicenter, cross-sectional survey in southwestern China. 2644 high-risk participants for stroke were enrolled in the year 2015. The primary outcome was new-onset ICH events during a five-year follow-up period. Multivariate logistic regression was performed to identify the association between carotid plaque and new-onset ICH. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between vulnerable carotid plaque and ICH.

Results: Among 2644 high-risk individuals enrolled, carotid plaques were found in 904 (34.2%) subjects, including 479 (18.1%) with stable plaques and 425 (16.1%) with vulnerable plaques. During a five-year follow-up period, 22 (0.83%) participants developed ICH. Vulnerable carotid plaque was associated with an increased risk of new-onset ICH in multivariable analyses (adjusted RR 3.72, 95 % CI 1.32 to 10.46, p=0.013). Stratified analyses and interaction analyses demonstrated the association between vulnerable carotid plaque and ICH was not changed by age, family history of stroke, hemorrhagic stroke and chronic disease, smoking, drinking, physical activity, BMI, antihypertensives, and antithrombotic drugs (all p for interaction>0.05). However, among the female cohort, participants with vulnerable plaques had a significantly higher risk of ICH compared with participants without vulnerable plaques (crude RR=9.8; 95%CI: 3.1-31.3, p<0.001; adjusted RR=26.3, 95%CI: 5.5-124.5, p<0.001), but not in man (p>0.05).

Conclusion: In Chinese individuals at high risk of stroke, vulnerable carotid artery plaques are associated with an increased risk of intracerebral hemorrhage independent of classical vascular risk factors, especially in female individuals.

Background: To determine the association of cardiovascular risk factors with the presence and anatomic location of CMBs and construct a factor-based evaluating model to predict a high CMBs burden.

Methods: We assessed the relation of age, male, various cardiovascular risk factors, medication use, stroke histories and white matter hyperintensities (WMH) to the presence and location of CMBs with univariate analysis and multiple logistic regression. Finally, we added risk factors for a high CMBs burden to a factor-based evaluating model score.

Results: 485 patients were included in our study. CMBs were more prevalent with advanced age, male sex, more cardiovascular risk factors and WMH. Alcohol use, hemorrhagic stroke history and the degree of deep white matter hyperintensity (DWMH) were independent predictors for a high CMBs burden (≥10). We finally structured a prediction model-HPSAD3 that consisted of hypertension, alcohol use, hemorrhagic stroke history and WMH to predict a high CMBs burden. The model-HPSAD3 has a higher positive predict value (77.08%) and negative predict value (75.89%) to predict a high CMBs burden when the cut-off score is 4.

Conclusions: Hypertension, alcohol use, hemorrhagic stroke history and WMH were added into the model- HPSAD3, and there was a higher possibility of patients with CMBs ≥10 when the score of HPSAD3 ≥4.

Background: The association between baseline red blood cell distribution width (RDW) and hemoglobin levels and outcomes after acute intracerebral hemorrhage (ICH) is not well studied. We aimed to investigate the association between baseline RDW and hemoglobin levels with early hematoma expansion (HE) and mortality at 3 months and 1 year in acute ICH patients.

Methods: A total of 393 ICH patients from January 2014 to February 2019 were included. Patients were divided into four groups based on quartiles of RDW and hemoglobin levels at admission, respectively. Logistic regression models were used to estimate the effect of the levels of RDW and hemoglobin on early HE (absolute hematoma growth >6 mL from baseline to follow-up) and allcaused mortality at 3 months and 1 year.

Results: There were no significant associations between baseline RDW and hemoglobin levels and early HE. The 3-month mortality (adjusted odds ratio [OR] 2.88; 95% confidence intervals [CI] 0.96-8.64) and 1-year mortality (adjusted OR 3.16, 95% CI 1.08-9.21) was significantly higher in patients with the highest RDW level (Q4) compared to those with the lowest RDW level (Q1). Moreover, patients with the lowest hemoglobin level were significantly associated with increased odds of all-cause mortality at 3-month (adjusted OR 3.95, 95% CI 1.26-12.4) and 1-year (adjusted OR 4.42, 95% CI 1.56-12.5) compared to those with highest hemoglobin level.

Conclusion: In patients with acute ICH, a higher level of RDW at admission significantly increased the risk of all-cause mortality at 1 year. Moreover, a decreased hemoglobin level at admission was also associated with a higher risk of all-cause mortality at 3 months and 1 year.

Background: Paeonol (Pae), the main active compound of the root of Paeonia albiflora, is efficacious in treating atherosclerosis (AS). Endothelial dysfunction is throughout the pathological progression of AS. It is expected that inhibition of Endothelial-to-mesenchymal transition (EndMT) will be a key target for AS treatment.

Objective: In this study, we investigated the molecular mechanism of the regulatory effect of Pae on EndMT in human umbilical vein endothelial cells (HUVECs).

Methods: Cell cytotoxicity, proliferation, and migration were detected by CCK-8, the wound healing assay, and EdU staining, respectively. The protein expressions were measured by Western blot or immunofluorescence staining. Immunofluorescence staining was performed to indicate endothelial cells undergoing EndMT in ApoE^-/- mice. In vitro TGF-β1-induced EndMT assays were performed in HUVECs and the effect of Pae was explored.

Results: We demonstrated that Pae could improve induced TGF-β1-EndMT in vivo and in vitro. Mechanism study revealed that Pae directly bonds to the activin-like kinase 5 (ALK5, also known as TGFβ type I receptor), inhibited downstream Smad2/3 phosphorylation, and thus alleviated EndMT. Notably, overexpression of ALK5 significantly reversed the inhibitory effect of Pae on EndMT in HUVECs.

Conclusion: Our results indicate that ALK5 is a promising druggable target for AS, and pharmacological regulation of ALK5-Smad2/3 signaling pathway with small-molecule holds great potential to benefit AS patients.

Background: Previous studies have shown that the neurological damage caused by middle cerebral artery occlusion (MCAO) is not only limited to local infarction but can also cause secondary damage in distant sites, such as the hypothalamus. 5-hydroxytryptamine (5-HT)/ 5-HT transporter (5-HTT) and 5-HT receptor 2A (5-HT2A) are important in the treatment of cerebrovascular diseases.

Objective: This study aimed to study the effect of electroacupuncture (EA) on the expression of 5- HT, 5-HTT, and 5-HT2A in the hypothalamus of rats with ischemic brain injury and to explore the protective effect and potential mechanism of EA on the secondary injury of cerebral ischemia.

Methods: Sprague-Dawley (SD) rats were randomly divided into three groups: sham group, model group, and EA group. The permanent middle cerebral artery occlusion (pMCAO) method was used to induce ischemic stroke in rats. In the EA group, the Baihui (GV20) and Zusanli (ST36) points were selected for treatment, which was administered once per day for two consecutive weeks. The neuroprotective effect of EA was evaluated by nerve defect function scores and Nissl staining. The content of 5-HT in hypothalamus was detected by enzyme linked immunosorbent assay (ELISA), and the expression of 5-HTT and 5-HT2A were detected by Western blot.

Results: Compared with that in the sham group, the nerve defect function score in the model group rats was significantly increased, the hypothalamus tissue showed obvious nerve damage, the levels of 5-HT and the expression of 5-HTT were significantly reduced, and the expression of 5-HT2A was significantly increased. After 2 weeks of EA treatment, the nerve defect function scores of pMCAO rats were significantly reduced, the hypothalamic nerve injury was significantly reduced, the levels of 5-HT and the expression of 5-HTT were significantly increased, and the expression of 5-HT2A was significantly decreased.

Conclusion: EA has a certain therapeutic effect on hypothalamic injury secondary to permanent cerebral ischemia, and its potential mechanism may be closely related to the upregulation of 5-HT and 5-HTT expression and the downregulation of 5-HT2A expression.

Background: Diabetic cardiac autonomic neuropathy (DCAN) is a serious diabetic complication with no approved pharmacological agents for its treatment. Parasympathetic system dysfunction characterized by vagal nerve damage is one of the major drivers of DCAN. The TRPC5 or transient receptor potential canonical 5 channel is a promising target in autonomic dysfunction; however, its role in vagal nerve damage and subsequent DCAN has not yet been elucidated. The present study investigated the role of the TRPC5 channel in DCAN using [N-{3-(adamantan-2-yloxy)-propyl}-3-(6-methyl-1,1-dioxo-2H-1λ⁶,2,4-benzothiadiazin-3-yl) propanamide)] or BTD, which is a potent TRPC5 activator.

Objectives: The role of the TRPC5 channel and its activator, BTD, was investigated in the treatment of parasympathetic dysfunction associated with DCAN.

Methods: Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin. The alterations in cardiac autonomic parameters in diabetic animals were assessed by heart rate variability, hemodynamic parameters, and baroreflex sensitivity. TRPC5's role in DCAN was investigated by treating diseased rats with BTD (1 and 3 mg/kg, i.p. for 14 days). BTD's beneficial effects in parasympathetic dysfunction were assessed by western blotting, estimating oxidative stress and inflammatory markers in the vagus nerve.

Results: BTD treatment (3 mg/kg, i.p.) once daily for 14 days ameliorated heart rate variability, hemodynamic dysfunction, and baroreflex sensitivity in diseased rats. BTD treatment down regulated TRPC5 expression by increasing the activity of protein kinase C in the vagus nerve. It also down-regulated the apoptotic marker CASPASE-3 and also exerted potent anti-inflammatory action on pro-inflammatory cytokines levels in the vagus.

Conclusion: BTD ameliorated parasympathetic dysfunction associated with DCAN by virtue of its TRPC5 modulatory, anti-inflammatory, and anti-apoptotic properties.

Introduction: The purpose of this study was to investigate the effects of bone marrow mesenchymal stem cells (BMSCs) exosomal miR-345-3p and tumor necrosis factor receptorassociated factor 6 (TRAF6) on cerebral ischemia reperfusion (CIR) injury. Exosomes (Exos) derived from BMSCs were isolated and identified. PC12 (rat pheochromocytoma) cells were used to establish an oxygen and glucose deprivation/reoxygenation (OGD/R) model.

Methods: Cell counting kit-8, TUNEL staining, lactate dehydrogenase staining, RT-qPCR, and western blotting were utilized for analyzing the functions of miR-345-3p about PC12 cells. Dualluciferase reporter experiment was then to confirm the link between miR-345-3p and TRAF6. Finally, using male SD rats, the middle cerebral artery occlusion (MCAO) model was constructed. Regulation of I/R damage in MCAO rats of miR-345-3p and TRAF6 were further explored in the changes of modified neurological severity score, cerebral infarction pictures, relative infarct volume, and histopathological changes. After OGD/R treatment, neuronal apoptosis was dramatically increased. After treatment with exosomal miR-345-3p, OGD/R-induced neuroapoptosis was dramatically inhibited. Exosomal miR-345-3p inhibited OGD/R-induced neuroapoptosis by downregulating the expression of TRAF6. However, the miR-345-3p inhibitor aggravated the changes caused by OGD/R.

Results: The corresponding regulations of miR-345-3p were reversed with TRAF6 overexpression. The animal experiments in vivo further verified that miR-345-3p ameliorated brain I/R injury in MCAO rats by targeting TRAF6.

Conclusion: This study found that BMSCs-exosomal miR-345-3p protected against CIR injury by decreasing TRAF6.

Objective: To investigate the changes in CT perfusion between symptomatic and asymptomatic patients with unilateral middle cerebral artery severe stenosis or occlusion.

Methods: A total of 64 consecutive patients with unilateral middle cerebral artery severe stenosis or occlusion admitted to the First Affiliated Hospital of Xinxiang Medical College from January 2019 to March 2022 were retrospectively analyzed and divided into the symptomatic group (n = 33), and the asymptomatic group (n = 31). Clinical data of the two groups were collected. Multivariate logistic regression analysis was performed to analyze the factors of symptomatic and asymptomatic MCA stenosis. A t-test was performed to compare the differences in cerebral perfusion parameters between the two groups.

Results: Multivariate logistic regression analysis indicated that glycosylated hemoglobin levels and high-density lipoprotein cholesterol levels were associated with the development of asymptomatic MCA severe stenosis or occlusion (odds ratio = 1.591 and 0.04, respectively). There were significant differences in CBV, MTT, and TTP between symptomatic and asymptomatic groups (p < 0.05). The CBF of the affected side in the symptomatic group was lower than that of the unaffected side (p < 0.05), whereas the asymptomatic group in CBF was not. Compared with the asymptomatic group, the CBF, MTT, and TTP of the affected side were significantly different (p < 0.05). In contrast, the cerebral perfusion parameters of the unaffected side were not significantly different (p > 0.05).

Conclusion: The use of CT perfusion imaging to analyze the alterations in cerebral perfusion parameters in patients with symptomatic and asymptomatic MCA severe stenosis or occlusion was helpful in clinical diagnosis and selecting treatment strategies and judging the development of the disease.