Uniform 3 nm-sized ceria nanoparticles can protect against ischemic stroke by scavenging reactive oxygen species (ROS) and reducing apoptosis. PEGylated ceria nanoparticles showed protective effects against ROS-induced cell death in vitro. Optimal doses of ceria nanoparticles reduced infarct volumes and the rate of ischemic cell death in vivo.

The two oxidation states of ceria nanoparticles, Ce and Ce , play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce is largely responsible for removing O and OH that are associated with inflammatory response and cell death. The synthesis is reported of 2 nm ceria-zirconia nanoparticles (CZ NPs) that possess a higher Ce /Ce ratio and faster conversion from Ce to Ce than those exhibited by ceria nanoparticles. The obtained Ce Zr O (7CZ) NPs greatly improve ROS scavenging performance, thus regulating inflammatory cells in a very low dose. Moreover, 7CZ NPs are demonstrated to be effective in reducing mortality and systemic inflammation in two representative sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS-related inflammatory diseases.

Background: Obesity is believed to increase the risks of ischemic stroke or coronary heart disease; however, regarding outcome after established vascular diseases, recent unexpected evidence has suggested that an increased body mass index (BMI) might have beneficial effects (obesity paradox). The aim of this study was to evaluate the independent association between BMI and long-term mortality after ischemic stroke. Methods: A total of 1,592 consecutive patients with ischemic stroke were prospectively included through our stroke cohort. In this study, the levels of BMI were classified based on guidelines for the Asian-Pacific population. Initial neurological severity was estimated by the National Institutes of Health Stroke Scale (NIHSS) score. Information on mortality was collected until the end of 2009, and the median follow-up period was 4 years. To examine the association between BMI and long-term mortality, we used Cox’s proportional regression analysis. Results: During follow-up, 23% of patients died. Linear regression analysis showed that the level of BMI was inversely related to initial neurological severity (p = 0.002). In the model of adjustment of age and gender using Cox’s proportional regression analysis, this inverse trend was also significant (reference, normal weight; hazard ratio of underweight, 2.45; overweight, 0.77; obesity, 0.60). However, after adjustment of all covariates, including initial neurological severity, only the harmful effect of underweight remained significant (2.79; 95% CI, 1.92–4.05); however, beneficial effects of overweight and obesity did not. Conclusion: Our study showed that an independent association between BMI and long-term mortality after ischemic stroke was found only in underweight patients. The obesity paradox phenomenon seems to be limited, and might not be interpreted as a direct causal relationship due to a strong association with initial neurological severity.

Background and Purpose-We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke. Methods-We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.0 years) enrolled consecutively from 11 nationwide stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a standard brain template set. Using multivariable analyses, we assessed the impact of major (age/hypertension) and minor risk factors on WMH variability. Results-We have produced a large reference data library showing the location and quantity of WMHs as topographical frequency-volume maps. This easy-to-use graphical reference data set allows the quantitative estimation of the severity of WMH as a percentile rank score. For all patients (median age=69 years), multivariable analysis showed that age, hypertension, atrial fibrillation, and left ventricular hypertrophy were independently associated with increasing WMH (0-9.4%, median=0.6%, of the measured brain volume). For younger (≤69) hypertensives (n=819), age and left ventricular hypertrophy were positively associated with WMH. For older (≥70) hypertensives (n=944), age and cholesterol had positive relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial fibrillation had negative relationships with WMH. For younger nonhypertensives (n=578), age and diabetes mellitus were positively related to WMH. For older nonhypertensives (n=328), only age was positively associated with WMH. Conclusions-We have generated a novel graphical WMH grading (Kim statistical WMH scoring) system, correlated to risk factors and adjusted for age/hypertension. Further studies are required to confirm whether the combined data set allows grading of WMH burden in individual patients and a tailored patient-specific interpretation in ischemic stroke-related clinical practice. Other risk factors such as diabetes mellitus, hyperlipidemia, atrial fibrillation, and smoking were inconsistently reported in the literature and seem less strongly associated with WMHs (Table I in the online-only Data Supplement). 3,[6][7][8][9][10] Despite a rapidly growing body of knowledge from population studies, substantial variability in WMH volume among individuals with similar cerebrovascular risk factors complicates a tailored interpretation of patient-specific implications of WMHs in daily clinical practice. [10][11][12] What is lacking is a comprehensive, quantitative study with substantial numbers, and robust methodology, which correlates WMHs to stroke risk factors so that the associations and interplay between risk factors can be better understood. Clinically, there have been no rigorous graphical and statistical reference data available for the individualized estimation of the relative severity (expressed as percentile ranks) of WMH burden adjusted for major risk factors (age/hypertension).In this study, we have combined (1) a la...

Einheitliche 3 nm große Cerdioxidnanopartikel können vor ischämischen Hirninfarkten schützen, indem sie reaktive Sauerstoffspezies (ROS) abfangen und die Apoptose zurückdrängen. PEGylierte Cerdioxidnanopartikel waren in vitro gegen ROS‐induzierten Zelltod wirksam. Optimale Dosen solcher Nanopartikel verringerten das Infarktvolumen und verlangsamten den ischämischen Zelltod.

Background and Purpose-Low cholesterol level is known to be associated with increased cerebral hemorrhage.However, the associations of hemorrhagic transformation (HTf) after acute ischemic stroke and the low levels of total cholesterol (TC) or low-density lipoprotein cholesterol (LDLC) are largely undiscovered. Methods-Of the 1034 patients with acute ischemic stroke who were consecutively admitted to our hospital, 377 patients with stroke attributable to large artery atherothrombosis (LAA; nϭ210) or cardioembolism (nϭ167) were selected for this study. Demographic and clinical information was collected and HTf was evaluated through follow-up T2*-weighted gradient-echo MRI performed usually within 1 week after stroke. Measurement of lipid parameters included TC, LDLC, high-density lipoprotein cholesterol, and triglyceride. Results-Of the 377 patients, HTf was noted in 74 patients (19.6%). When patients were divided into 4 groups according to their TC and LDLC levels, the incidence of HTf was significantly elevated in the lowest quartile of each TC (PϽ0.01) and LDLC (PϽ0.01) level in LAA subgroup, but not in cardioembolism. After adjusting covariates, a low level of LDLC (OR, 0.46 per 1 mmol/L-increase; 95% CI, 0.22-0.98) was independently associated with HTf in LAA, but not in cardioembolism. There was no significant association between low levels of TC (OR, 0.63 per 1 mmol/L-increase; 95% CI, 0.35-1.15) and HTf in LAA. Conclusions-Low levels of LDLC, and possibly TC, are associated with greater risk of hemorrhagic transformation after acute ischemic stroke attributable to LAA.

BackgroundCerebral microbleeds (MBs) are understood as an important radiologic marker of intracerebral hemorrhage. We sought to investigate the temporal changes of MBs and clinical factors associated with the changes using long-term follow-up MRI.Methods/Principal FindingsFrom October 2002 to July 2006, we prospectively enrolled patients with stroke or transient ischemic attack, and followed-up their brain MRIs with an interval >12 mo. We compared demographic factors, vascular risk factors, laboratory findings, and radiologic factors according to the presence or changes of MBs. A total of 224 patients successfully completed the follow-up examinations (mean, 27 months). Newly developed MBs were noted in 10 patients (6.8%) among those without MBs at baseline (n = 148), and in those with MBs at baseline (n = 76), the MB count had decreased in 11 patients (14.5%), and increased in 41 patients (53.9%). The estimated annual rate of change of MB numbers was 0.80 lesions per year in all patients, a value which became greater in those patients who exhibited MBs at baseline (MBs≥5, 5.43 lesions per year). Strokes due to small vessel occlusion and intracerebral hemorrhage, as well as white matter lesions were independently associated with an increased MB count, whereas the highest quartile of low-density lipoprotein (LDL) cholesterol was associated with a decreased MB count.ConclusionDuring the follow-up period, most of MBs showed dynamic temporal change. Symptomatic or asymptomatic small vessel diseases appear to act as risk factors while in contrast, a high level of LDL cholesterol may act as a protective factor against MB increase.

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