Lulu Xiao

Coronary heart disease and chronic periodontitis: is polymorphism of interleukin-6 gene the common risk factor in a Chinese population?

OBJECTIVES Coronary heart disease (CHD) and chronic periodontitis (CP) both are multifactorial chronic diseases and related to inflammation. Interleukin-6 (IL-6) plays an important role in the pathogenesis of inflammatory diseases. The purpose of the study was to investigate the association among IL-6 gene polymorphisms, CP and CHD susceptibility in a Chinese population. MATERIAL AND METHODS   The investigation was conducted as a case-control study involving 505 individuals: 113 patients with CHD and CP, 84 patients with CHD, 178 patients with CP and 130 control individuals. The polymorphisms of IL-6 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Relationships between the distributions of the genotypes and risk factors were also assessed. RESULTS   Mutations at the loci -174 G/C, -597 G/A of IL-6 were rare in a Chinese population. No significant difference for IL-6-572C/G polymorphism was detected among moderate CP group, severe CP group and control (P = 0.312 and 0.481), significant differences were found between CHD groups and non-CHD groups (P ≤ 0.001). After adjustment for CHD risk factors, the G allele resulted in an increased risk (OR = 1.676-1.856), the GG/CG genotype was nearly two times higher risk compared to CC genotype (OR = 2.010-2.136). CONCLUSIONS   IL-6-572C/G polymorphism did not correlate with CP susceptibility, but might be a potential risk factor for CHD in a Chinese population.

Chronic Kidney Disease in Patients With Lacunar Stroke Association With Enlarged Perivascular Spaces and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

Background and Purpose— The relationship between chronic kidney disease and cerebral small vessel disease (cSVD), especially enlarged perivascular spaces (EPVS), has not been fully understood. This study aimed to investigate the association of chronic kidney disease and EPVS, as well as the total burden of cSVD on magnetic resonance imaging, expressed by the simultaneous presence of multiple markers of cSVD, among patients with first-ever lacunar stroke. Methods— Four hundred and thirteen consecutive patients were prospectively enrolled. Centrum semiovale and basal ganglia EPVS on T2-weighted magnetic resonance imaging, as well as other imaging markers of cSVD, including lacune, white matter lesions, and cerebral microbleeds, were rated using validated scales. Chronic kidney disease was defined as either reduced estimated glomerular filtration rate or the presence of proteinuria. Results— After adjustments for potential confounders by logistic regression, proteinuria and impaired estimated glomerular filtration rate were correlated with the severity of EPVS in both centrum semiovale (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.19–5.64 and OR 2.37; 95% CI 1.19–4.73) and basal ganglia (OR 5.12; 95% CI 2.70–12.10 and OR 4.17; 95% CI 2.08–8.37). A similar association was also found between proteinuria and low estimated glomerular filtration rate levels and the comprehensive cSVD burden (OR 2.13; 95% CI 1.10–4.14 and OR 5.59; 95% CI 2.58–12.08). Conclusions— Proteinuria and impaired estimated glomerular filtration rate are associated with increasing EPVS severity and, furthermore, accumulated magnetic resonance imaging burden of cSVD in patients with first-ever acute lacunar stroke.

Asymmetrical cortical vessel sign on susceptibility‐weighted imaging: a novel imaging marker for early neurological deterioration and unfavorable prognosis

Susceptibility‐weighted imaging (SWI) is a high spatial resolution technique that can indirectly demonstrate increased cerebral oxygen extraction. Our aim was to assess whether asymmetric cortical vessel sign (ACVS) on SWI could be associated with early neurological deterioration (END) as well as 90‐day unfavorable outcome in patients with acute ischaemic stroke.

Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway

Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 small interfering RNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with Cav-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, phospho-Raf, and phospho-ERK were sequestered in Cav-1 small interfering RNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway is required for the Cav-1s prosurvival role. Together, these findings support Cav-1 as a checkpoint for the in hypoxia-induced astrocyte apoptosis and warrant further studies targeting Cav-1 to treat hypoxic-ischemic brain injury.

Microbleeds in ischemic stroke are associated with lower serum adiponectin and higher soluble E-selectin levels.

BACKGROUND Cerebral microbleeds (CMBs) are the important indicators of cerebral small vessel disease. However, it is still unclear whether endothelial dysfunction is involved in CMBs. In this study, we performed a prospective study to investigate the correlation between sE-selectin (soluble E-selectin) or adiponectin and the prevalence of CMBs. METHODS We recruited 133 consecutive patients with first-ever ischemic stroke for this study. Finally, 126 patients were analyzed. The number and presence of CMBs were detected and evaluated on susceptibility-weighted magnetic resonance imaging within two weeks after symptom onset. We assessed the serum levels of adiponectin and sE-selectin for patients. RESULTS CMBs were detected in 63 subjects (50%) within 126 patients and more prevalent in mixed brain regions (55.6%). In binary logistic regression analysis, each 1SD-increase in adiponectin level was significantly conversely associated with the prevalence of CMBs after adjusting for age, sex and cardiovascular risk factors (OR = 0.55; 95% CI: 0.36-0.84); but sE-selectin was significantly positively associated with the prevalence of CMBs (OR = 1.09; 95% CI: 1.02-1.15). Furthermore, partial correlation analyses showed that sE-selectin remained significantly associated with and correlated conversely to adiponectin (r = -0.452, p = 0.001). CONCLUSIONS Endothelial injury may play a role in the pathogenesis of CMBs, and serum levels of adiponectin and sE-selectin were closely related to CMBs. Adiponectin might be protective for the prevalence of CMBs.

From clinical to tissue-based dual TIA Validation and refinement of ABCD3-I score

Objective: To investigate whether dual tissue-defined ischemic attacks, defined as multiple diffusion-weighted imaging lesions of different age and/or arterial territory (dual DWI), are an independent and stronger predictor of 90-day stroke than dual clinical TIAs (dual TIA). Methods: Consecutive patients with clinically defined TIA were enrolled and assessed clinically and by MRI within 3 days. The predictive ability of the ABCD clinical factors, dual TIA, and dual DWI was evaluated by means of multivariate logistic regression. Results: Among 658 patients who were included in the study and completed 90 days of follow-up, a total of 70 patients (10.6%) experienced subsequent stroke by 90 days. Multivariate logistic regression indicated that dual DWI was an independent predictor for subsequent stroke (odds ratio 4.64, 95% confidence interval 2.15–10.01), while dual TIA was not (odds ratio 1.18, 95% confidence interval 0.69–2.01). C statistics was higher when the item of dual TIA in ABCD3-I score was replaced by dual DWI (0.759 vs 0.729, p = 0.035). The net reclassification value for 90-day stroke risk was also improved (continuous net reclassification improvement 0.301, p = 0.017). Conclusion: Dual DWI independently predicted future stroke in patients with TIA. A new ABCD3-I score with dual DWI instead of dual clinical TIA may improve risk stratification for early stroke risk after TIA.

Validation of NINDS-CSN neuropsychological battery for vascular cognitive impairment in Chinese stroke patients

BackgroundThe NINDS-Canadian Stroke Network (NINDS-CSN) recommended a neuropsychological battery of three protocols to diagnose vascular cognitive impairment (VCI), however, due to culture and language differences, the battery cannot be directly used in China. Validation of the battery in mandarin Chinese is lacking. Our study investigated the reliability and validity of the adapted Chinese versions of the battery in stroke patients with high probability of VCI.MethodsFifty mild stroke patients (median of National Institute of Health Stroke Scale [NIHSS] score, 2) and 50 stroke-free normal controls were recruited. All subjects’ demographics, clinical history, and stroke severity were recorded. The NINDS-CSN neuropsychological protocols were adapted into the Chinese versions. External validity, defined as the ability of the protocol summary scores to differentiate stroke patients from controls, was determined using the area under the curve (AUC) of the receiver operating characteristics curve. We also evaluated internal consistency and intra-rater reliability.ResultsStroke patients performed significantly poorer than controls on all three protocols (F statistics between 24.9 and 31.4, P < 0.001). External validity evaluated by AUCs was 0.88 (95% confidence interval [CI], 0.81-0.95), 0.88 (95% CI, 0.81-0.94), and 0.86 (95% CI, 0.79-0.94) for the 60-min, 30-min and 5-min protocols, respectively. Cronbach’s alpha of the cognitive tests was 0.87 for all subjects. Intra-rater reliability was acceptable with intraclass correlation coefficients 0.90, 0.83 and 0.75 for the 60-min, 30-min and 5-min protocols, respectively.ConclusionsThe adapted Chinese versions of three NINDS-CSN neuropsychological protocols were valid and reliable for assessing VCI in Chinese patients with mild stroke.

Correlation between cerebral microbleeds and S100B/RAGE in acute lacunar stroke patients

BACKGROUND AND PURPOSE S100B and its scavenger, soluble receptor for advanced glycation end products (sRAGE), participate in various acute and chronic brain disorders. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is unclear. The purpose of this study was to investigate the relationship of CMBs with plasma S100B and sRAGE. METHODS A cohort of 147 consecutive patients with first-ever acute lacunar stroke was prospectively enrolled. We collected demographic, clinical, and laboratory data, including plasma levels of S100B and sRAGE, and presence and number of CMBs using susceptibility-weighted imaging (SWI). Associations between plasma S100B, sRAGE levels and the presence, number, and location of CMBs were determined. RESULTS CMBs were present in 58 patients (39.5%). Each 1SD-increase in S100B and sRAGE levels was significantly associated with presence of CMBs (adjusted odds ratio [OR], 3.06; 95% confidence interval [CI], 1.81-5.17 and adjusted OR, 0.29; 95% CI, 0.16-0.53; respectively) and number of CMBs (adjusted relative risk [RR], 4.07; 95% CI, 3.60-5.65 for S100B and RR 0.34; 95% CI, 0.25-0.46 for sRAGE). When stratified by location, plasma S100B and sRAGE levels were similarly associated with presence of deep CMBs (adjusted OR, 3.65; 95% CI, 1.99-6.69 and adjusted OR, 0.23; 95% CI, 0.12-0.46; respectively), but not with strictly lobar CMBs. CONCLUSIONS Higher levels of S100B and lower levels of sRAGE are independently associated with presence and number of CMBs in patients with first-ever acute lacunar stroke, particularly in those with deep CMBs.

Lower Serum Caveolin-1 Is Associated with Cerebral Microbleeds in Patients with Acute Ischemic Stroke

Caveolin-1 (Cav-1) plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD) in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs), silent lacunar infarcts (SLIs), and white matter hyperintensities (WMHs). After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77–9.30). However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59–10.25) and with multiple CMBs (OR: 3.18, 95% CI: 1.16–8.72). These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD.

Large-Vessel Occlusion Is Associated with Poor Outcome in Stroke Patients Aged 80 Years or Older Who Underwent Intravenous Thrombolysis

OBJECTIVE We aimed to investigate the association between large-vessel occlusion (LVO) and functional outcome in elderly stroke patients treated with intravenous (IV) tissue plasminogen activator (tPA). METHODS This was a retrospective study of acute ischemic stroke patients who received IV tPA within 4.5 hours after stroke onset between 2007 and 2013. Patients were categorized into 2 groups based on age (≥80 or < 80 years). LVO was evaluated by computed tomography angiography (CTA) before thrombolysis. Favorable outcome was defined as a modified Rankin Scale (mRS) score of 2 or lower at 3 months, or equal to the prestroke mRS score. RESULTS Of 359 thrombolysis patients, 175 patients with CTA before a standard dose of IV tPA therapy (0.9 mg/kg body weight; maximum 90 mg) were included. Sixty-five patients were in the group aged 80 years or above with a median age of 84 (interquartile range: 82.5, 86) years. LVO was observed more often in the group with unfavorable outcome compared with the group with favorable outcome in older stroke patients (60.6% versus 21.9%, P = .002). The baseline National Institutes of Health Stroke Scale (NIHSS) score (odds ratio .864; 95% confidence interval [CI], .779-.959; P = .006) and LVO (odds ratio .233; 95% CI, .059-.930; P = .039) were independent associative factors for the unfavorable outcome in older patients treated with IV tPA after adjustment for patient characteristics. CONCLUSIONS The baseline NIHSS score and LVO were independent predictors for functional outcome in elderly stroke patients received IV tPA.