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Abstract Aims Atherosclerosis is more prevalent in Asian population. This distinct etiology of stroke might disadvantage Asian patients when applying. mechanical thrombectomy (MT). The purpose of this research was to evaluate the efficacy and safety of MT in a cohort of Chinese patients with acute ischemic stroke. due to large artery atherosclerosis (LAA). Methods and results A total of 649 patients treated with MT were included. Patients were classified according to etiology of stroke as LAA and cardioembolism ones. Successful revascularization was defined as modified Thrombolysis in Cerebral Infarction (mTICI) grade ≥ 2b. Favorable outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at 90 days. Logistic regression was used to identify predictors for functional outcomes. The patients with stroke of LAA etiology had significantly higher rate of favorable functional outcome (50.2% vs 36.5%, p <.001) and good collateral (grade of ASITN/SIRI: 2–3) (58.8% versus 43.2%, p <.001), and lower median baseline National Institutes of Health Stroke Scale score (NIHSS) (15.6 versus 18.2, p <.001), compared to patients with stroke of cardioembolism etiology. There was no significant difference in the rate of successful postprocedural mTICI between groups (84.5% versus 83.2%, p =.671). Rates of symptomatic intracranial hemorrhage (20.0% versus 11.7%, p =.004) and mortality (31.8% versus 18.8%, p <.001) within 3 months were notably higher in the cardioembolism group than that in the LAA group. Conclusion Mechanical thrombectomy may be more efficacious in treating acute ischemic stroke of LAA etiology than that of cardioembolism etiology. Highlights • Effects of mechanical thrombectomy(MT) were studied in patients with LAA stroke. • High rate of successful postprocedural mTICI and good collateral were achieved. • Low rates of symptomatic intracranial hemorrhage and mortality were observed. • High rate of favorable functional outcome at 3 months was obtained. • MT is efficacious in treating acute ischemic stroke of LAA etiology. [ABSTRACT FROM AUTHOR]

Purpose Prostaglandin-Endoperoxide Synthase 1 (PTGS1) and smoking may play important roles in aspirin nonresponsiveness, but the effect of their interaction on stroke outcomes remains largely unknown. We examined the effects of PTGS1 polymorphisms, smoking status, and their interaction on functional outcomes in a cohort of Chinese Han patients with stroke during aspirin therapy. Methods A total of 617 ischemic stroke patients taking aspirin were enrolled. Three single nucleotide polymorphisms (SNPs) rs1330344, rs3842788, and rs5788 in PTGS1 were determined for genotyping. Poor functional outcomes were defined as a modified Rankin Scale (mRS) of 3–6 at 90-day follow-up. The influence of PTGS1 gene-smoking interaction on functional outcomes was examined. Results Poor functional outcomes occurred in 145 (23.5%) patients. When adjusting multiple factors by logistic regression, CC genotype of rs1330344 was associated with poor functional outcomes (risk ratio [RR] = 1.73; 95% confidence interval [CI]: 1.17–2.37). A similar connection was found in the CGC haplotype (RR = 1.40; 95% CI: 1.08–1.77). Furthermore, we found a significant interaction between rs1330344 and smoking status ( P interaction = 0.018); the interaction effect between the PTGS1 haplotype and smoking also showed statistical significance ( P interaction = 0.040). Conclusions In Chinese Han stroke patients with aspirin therapy, the adverse effect of PTGS1 polymorphisms on functional outcomes may be modulated by the smoking status. PTGS1 gene-smoking interaction might in part reflect the heterogeneity in the prognosis of patients treated with aspirin. [ABSTRACT FROM AUTHOR]

Background Despite clopidogrel has been widely applied to patients with ischemic stroke combined with aspirin, decreased metabolic activation of clopidogrel still occurs because of genetic variations in CYP2C19 . Methods Three hundred twenty-one patients completed a genetic test for CYP2C19 loss of function (LOF) alleles in hospital. Cox regression models were used to assess the relationship between CYP2C19 genotypes with the primary endpoint, which was a composite of nonfatal ischemic stroke, myocardial infarction, or vascular death. Functional outcome was measured by the modified Rankin Scale (mRS) at 3 months, 6 months and 12 months intervals. Binary logistic regression was used to analyze the correlation between poor functional outcome and CYP2C19 LOF alleles. Results The CYP2C19 LOF alleles were independently associated with the primary endpoint. There was no significant association between poor functional outcome and CYP2C19 LOF allele ( *2 and *3 ) in overall patients. After the participants were stratified by stent treatment into two groups, the polymorphisms of CYP2C19 had significant impact on poor prognosis at 3 months and 6 months but not at 12 months in patients without stent. No correlation was found in patients with stent. Conclusions The CYP2C19 LOF alleles may increase the recurrent risk of ischemic events. The polymorphisms of CYP2C19 may be predictors of poor functional outcome of patients without stent, and the effect may be weakened by time. [ABSTRACT FROM AUTHOR]

Background and purpose The low rate of hypertension control is a major cause for the high rate of stroke morbidity and mortality in China. This study aimed to evaluate the impacts of premorbid hypertension treatment on the functional outcomes in patients with acute ischemic stroke and hypertension. Methods Patients with first-ever ischemic stroke and hypertension were screened from Nanjing Stroke Registry Program for eligibility. Functional outcomes were followed at 3 months with modified Rankin Scale (mRS). A good functional outcome was defined as mRS ≤ 2. Potential factors associated with good functional outcomes were analyzed with multivariate logistic regression. Results A total of 660 patients with both ischemic stroke and hypertension were included, of whom 284 (43.0%) were on antihypertensives before stroke. In univariate analysis, more patients with hypertension treatments had good outcomes than those without (47.7% vs 31.0%, P = 0.0001). After adjusted for age, heart diseases, baseline stroke severity, systolic blood pressure at admission, pneumonia, intravenous thrombolysis, and hospital stay, multivariate logistic regression indicated that premorbid hypertension treatment was related to an increased likelihood of good functional outcomes (OR: 2.21, 95% CI: 1.30 to 3.74, P = 0.003). Conclusions Less than half of the Chinese patients with hypertension were on drug treatment prior to stroke onset. Lack of premorbid hypertension treatment may have deteriorated functional outcomes of stroke. These findings emphasized the importance of improving hypertension treatment in Chinese, especially in whom at high risk of cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Recently, a genome-wide association study (GWAS) identified two common variants (rs12425791 and rs11833579) on Chromosome 12p13 that confer risk for stroke. The aim of this study was to evaluate whether these two variants are associated with risk of large artery atherosclerotic (LAA) stroke in a Chinese population. Rs12425791 and rs11833579 were genotyped using the improved multiple ligase detection reaction in 423 patients with LAA stroke and 423 healthy controls. We found a statistically significantly increased risk of LAA stroke associated with the rs12425791AA genotype (OR = 2.28, 95% CI = 1.15–4.51) and rs11833579 AA genotype (OR = 1.92, 95% CI = 1.16–3.15) compared with their GG genotype. When we evaluated these two polymorphisms together, we found that the combined genotypes with 3–4 variant alleles (rs12425791A and rs11833579A) were associated with an increased risk of LAA stroke (OR = 2.06, 95% CI = 1.26–3.36) compared to 0–2 variants. Moreover, genotype–phenotype correlation analysis showed that rs12425791AA and rs11833579AA carriers had significantly decreased NINJ2 mRNA expression levels in the Chinese population ( P = 0.003 for rs12425791 and P = 0.005 for rs11833579). These results suggested that the rs12425791 and rs11833579 polymorphisms on Chromosome 12p13 may be associated with the risk of LAA stroke and might be used as candidate biomarkers for LAA stroke susceptibility. [ABSTRACT FROM AUTHOR]

Bax interacting factor-1 (Bif-1), a multifunctional protein, can regulate cell apoptosis and autophagy. Up-regulation of Bif-1 expression has been associated with neuronal survival. Moreover, several studies have reported that Bif-1 is involved in ischemic stroke. However, the specific function of Bif-1 in cerebral ischemia-reperfusion (I/R) injury is not well understood. The aim of this study is to expose the potential protective effect of Bif-1 against cerebral I/R injury and its related mechanism. In the current study, we showed that adenovirus-mediated Bif-1-overexpression promoted oxygen and glucose deprivation followed by reperfusion (OGD/R)-treated cortical neurons' survival and reduced the cell apoptotic rate. We found that caspase-3 activity was inhibited by Bif-1 overexpression. In addition, we observed that Bif-1 overexpression induces cell autophagy, and the autophagy-specific inhibitor 3-Methyladenine (3-MA) attenuates cell survival. Interestingly, knockdown of Bif-1 resulted in attenuation of neuron survival, promotion of cell apoptosis and suppression of cell autophagy in neurons. In addition, knockdown of Bif-1 inhibited ERK1/2 activation. Our observations implicated Bif-1 as a novel target of cerebral I/R injury and played a neuroprotective effect via promoting cell survival and reducing apoptosis. [ABSTRACT FROM AUTHOR]

Background Maladjustment of matrix metalloproteinases (MMPs) results in cerebral vasculature and blood–brain barrier dysfunction, which is associated with small vessel disease (SVD). This study was to aim at evaluating correlations between matrix metalloproteinase-2 and 9 single nucleotide polymorphisms and the risk of SVD. Methods A total of 178 patients with SVD were enrolled into this study via Nanjing Stroke Registry Program (NSRP) from January 2010 to November 2011. SVD patients were further subtyped as isolated lacunar infarction (ILI, absent or with mild leukoaraiosis) and ischemic leukoaraiosis (ILA, with moderate or severe leukoaraiosis) according to the Fazekas scale. 100 age- and gender-matched individuals from outpatient medical examination were recruited as the control group. The genotypes of MMP-2-1306 T/C and MMP-9-1562 C/T were determined by the TaqMan method. Results Of 178 SVD patients, 86 and 92 patients were classified as ILI and ILA, respectively. Comparison analysis between SVD patients and controls revealed a significant correlation between SVD and hypertension, as well as a prevalence of hypertension in ILA. Further genotype analysis showed that the frequency of MMP-2-1306 CC genotype was higher in ILA patients than in controls ( P = 0.009, χ 2 test; P = 0.027, the multiple test with Bonferroni correction). Finally, logistic regression analysis with adjustment of age, sex and vascular risk factors showed that the MMP-2-1306 T/C polymorphism was an independent predictor for ILA (OR: 2.605; 95% confidence interval [CI], 1.067–6.364; P = 0.036). Conclusion Our findings suggest that the MMP-2-1306 T/C polymorphism is a direct risk factor for ILA. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a considerable cause of mild cognitive impairment and dementia. Intranasal administration of nerve growth factor (NGF) has previously been found to improve cognitive function after TBI, but the mechanism remains unclear. This study aimed to investigate the effects of intranasal NGF on the tau hyperphosphorylation following TBI. A modified Feeney's weight-drop model was used to induce TBI. Rats were randomly divided into control group, TBI group, TBI + NGF group, TBI + PDTC group and TBI + IL-1ra group. Rats in TBI + NGF group were administered with NGF (5 μg/d) for 3 d before surgery. Hyperphosphorylated tau protein was remarkable in the peri-contusional cortex area with TBI. Both western blotting and immunostaining results displayed intranasal pretreatment of NGF significantly reduced tau phosphorylation. To evaluate the underlying mechanism, the levels of glycogen synthase kinase 3β (GSK-3β), interleukin-1β (IL-1β), and the DNA binding activity of nuclear factor-κB (NF-κB) were assayed. NGF markedly inhibited GSK-3β. NGF also reduced TBI-induced elevation of IL-1β and NF-κB DNA binding activity. Furthermore, PDTC and IL-1ra were injected to prove a potential signaling pathway among NF-κB, IL-1β and GSK-3β. Taken together, these findings demonstrated that intranasal NGF could effectively attenuate the hyperphosphorylation of tau after TBI, which might involve an integrated signaling pathway related to NF-κB. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Background and Purpose: Our previous study found that cortical gray matter (cGM) volume predicted vascular cognitive impairment independent of age-related white matter changes (WMC). We aimed to investigate predictors for cGM volume in ischemic stroke patients with confluent WMC. Methods: One-hundred post-stroke patients with confluent WMC were recruited into the study. All volumetric measures were standardized by intracranial volume as volume ratio. Univariate analyses and multivariate linear regression models were used to test relationship of cGM volume with basic demography, vascular risk factors, APOE status, WMC volume (periventricular and deep WMC), infarct measures (volume, number and location) and microbleed (number, presence and location). Results: After controlling for significant variables in the univariate analyses, multivariate linear regression models found that old age (β =−0.288, p =0.001), low triglyceride (β =0.194, p =0.027), periventricular WMC (PVWMC) (β =−0.392, p <0.001) and presence of thalamic microbleed (β =−0.197, p =0.041) were independently predictive of less cGM volume ratio. Conclusions: Age, PVWMC and left thalamic microbleed predict less cGM volume. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Background: Warfarin use increases mortality in patients with intracerebral hemorrhage (ICH). Larger hematoma volume and infratentorial location are both major determinants of poor outcome in ICH. Although warfarin-associated intracerebral hemorrhages have greater volumes, there is uncertainty about the effects of location. We aimed to investigate the influence of warfarin on hematoma volume and location. Methods: We conducted a retrospective study of all patients hospitalized for ICH at a large stroke center from October 2007 to January 2012. Initial CT scans were used to quantify hematoma volumes using the computer-assisted planimetric analysis. Univariate and multivariable analyses determined the influence of warfarin on hemorrhage location. Median regression analysis was performed to estimate the effects of INR on hematoma volumes. Results: We included 404 consecutive patients with ICH of whom 69 were on warfarin. Patients on warfarin had larger hematoma volumes (median 23.9mL vs. 14.2mL; P =0.046). In patients excessively anticoagulated with warfarin (defined as INR>3.0), compared with those in the therapeutic range, brainstem ICH was more frequent (24.0% vs. 6.1%; P =0.005). Patients with INR>3.0 had increased odds of infratentorial hemorrhage (OR 3.63; 95% CI 1.52–8.64; P =0.004) when compared to non-warfarin ICH patients. After adjustment for hematoma location, there was no significant association between INR and hematoma volume. Conclusions: Patients with warfarin-associated ICH have a predilection for brainstem ICH. After adjustment for ICH location, no relationship between admission INR and hematoma volume was found. [Copyright &y& Elsevier]

Abstract: Background and purpose: The lesion patterns and mechanisms of ischemic stroke caused by extracranial internal carotid artery (EICA) stenosis are well understood. The prognosis of intracranial internal carotid artery (IICA) stenosis is very poor. However, little is known about lesion patterns and mechanisms of cerebral infarcts caused by IICA stenosis. The objective of this study was to investigate the lesion patterns and mechanisms of infarcts produced by severe IICA stenosis and compare it with that produced by severe EICA stenosis. Methods: We recruited 62 patients with acute cerebral infarcts who fulfilled the following criteria: 1) lesions of acute infarcts were verified by diffusion-weighted imaging (DWI) performed within 1week of stroke onset; 2) infarct lesions were located within the territory of unilateral internal carotid artery (ICA); 3) infarcts were definitely caused by severe atherosclerosis stenosis (stenosis rate of 70%–99%) of the ipsilateral IICA or EICA, with all other potential causes of stroke being entirely excluded. According to the distributions of infarct lesions in the arterial territory of the ICA displayed on DWI, lesion patterns were classified as either 1) single infarct [perforating artery infarct (PAI), pial artery infarct (PI) or border-zone infarct (BZI)], or 2) multiple infarcts (a combination of types described above). Results: There were 29 patients with ischemic stroke caused by severe IICA stenosis, and 33 patients with stroke caused by severe EICA stenosis. Single BZI (14/29, P =0.015), and infarcts involving the border zone (19/29, P =0.021) or the internal border zone (13/29, P =0.013) were identified more often in patients with IICA stenosis compared to those with EICA stenosis. PI and/or PAI (22/32, P =0.021) were identified more often in patients with EICA stenosis. Conclusions: Lesion patterns in patients with severe IICA stenosis were different from those with severe EICA stenosis. The hypoperfusion mechanism leading to BZI was more important for patients with severe IICA stenosis than for those with severe EICA stenosis. Embolisms leading to PI and/or PAI were more important for patients with severe EICA stenosis. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the relationship between plasma C-reactive protein (CRP) and the risk for cognitive deterioration and development of dementia in patients with mild cognitive impairment (MCI). Methods: Elderly Chinese patients with suspected cognitive impairment were screened. A total of 168 patients who met the criteria for MCI were enrolled. Plasma CRP levels were measured at baseline. The global cognitive functions were assessed at baseline and during follow-up periodically with Mini-Mental State Examination (MMSE). All enrolled patients were followed and evaluated regularly for 2 years to determine if the patients developed dementia. Results: Of the 168 patients with MCI diagnosed at baseline, 14 (8.3%) deceased, 13 (7.7%) lost to follow-up, and 58 (34.5%) developed dementia during follow-up. MMSE score of the enrolled patients declined significantly during follow-up (22.1±3.0 vs 18.6±5.5, P <0.001). MMSE score was significantly lower for the patients with high CRP levels than that for those with low plasma CRP levels (−4.9±5.4 vs −3.2±4.2, P <0.05). Patients with high plasma CRP level had an increased risk for dementia and vascular dementia as compared with patients with low level of plasma CRP (Log rank test, P <0.05). Conclusion: High plasma CRP level was associated with accelerated cognitive decline and increased risk for dementia in patients with MCI. [Copyright &y& Elsevier]