Edaravone Combined with Clopidogrel Is Beneficial to Improve Efficacy, Neurological Impairment, and Life Function in Acute Cerebral Infarction Patients.

OBJECTIVE: This research aimed at investigating the efficacy of edaravone combined with clopidogrel on acute cerebral infarction (ACI) and its influence on the neurological deficit and life function. METHODS: Totally, 154 ACI cases were included and then divided into the control group (CG) (n = 71) and research group (RG) (n = 83) according to the treatment methods. Patients in the CG were treated with clopidogrel alone, and those in the RG were under edaravone-clopidogrel combination therapy. The efficacy, adverse reactions, NIHSS score, cerebral hemodynamic indexes, and Fugl-Meyer scale (FMA) and Barthel index (BI) of activities of daily living (ADL) scores were observed. RESULTS: Compared with before treatment, the symptoms of both groups were improved after treatment: the NIHSS scores decreased, FMA and ADL scores increased, and cerebral hemodynamic indexes were improved. Compared with the CG, the efficacy and cerebral hemodynamic indexes of the RG were better, the adverse reactions were equivalent, the NIHSS score was lower, and the ADL and FMA scores were higher. CONCLUSION: Edaravone combined with clopidogrel can effectively treat ACI and improve the neurological deficit and life function of patients.

Design and development of novel thiazolidin-4-one-1,3,5-triazine derivatives as neuro-protective agent against cerebral ischemia-reperfusion injury in mice via attenuation of NF-ĸB.

The present study enumerates the discovery and development of novel thiazolidin-4-one-1,3,5-triazine as neuro-protective agent against cerebral ischemia-reperfusion injury in mice. These compounds showed significant inhibition of NF-ĸB transcriptional activity in LPS-stimulated RAW264.7 cells, displaying compound 8k as most potent inhibitor among the tested derivative. The compound 8k was further studied in in vivo middle cerebral artery occlusion (MCAO) mice model for neuro-protective action. Results suggest that compound 8k causes attenuation of inflammation (TNF-α, IL-ß, and IL-6), oxidative stress (SOD, GSH, and MDA), and apoptosis (Bcl-2, Bax, and cleaved caspase-3) in MCAO mice in concentration-dependent manner. Collectively, our results documented that compound 8k pre-treatment protects cerebral I/R. This novel lead scaffold may be helpful for investigation of new neuro-protective agent by inactivation of NF-ĸB.

Genetic variants in ALDH2 predict risk of ischemic stroke in a Chinese population.

BACKGROUND AND PURPOSE: Genome-wide association studies discovered a novel correlation between chromosome 12q24 and ischemic stroke in European populations. This study aimed to determine whether two genetic variants (rs10744777 and rs886205) on chromosome 12q24 can modify the risk of ischemic stroke in Chinese population. METHODS: We recruited 1195 patients with ischemic stroke and 642 healthy Chinese individuals. The rs10744777 and rs886205 polymorphisms in aldehyde dehydrogenase2 (ALDH2) was genotyped and compared using multivariate logistic regression. RESULTS: The genotype of rs10744777 (CT/TT) was associated with risk of ischemic stroke in males (OR = 1.99, 95% CI = 1.15-3.42, P = 0.013). In contrast, no significant correlation was found in females. Haplotype analysis indicated that haplotype "TA" was associated with increased ischemic stroke risk (OR = 1.85, 95% CI = 1.10-3.12, P = 0.042). Further subtype analysis demonstrated that the rs10744777 (CT/TT) genotype was strongly associated with large artery atherosclerosis subtype in males (OR = 2.27, 95% CI = 1.30-3.95, P = 0.004). After three months follow-up, we found a poorer functional outcome of ischemic stroke associated with the rs886205 GA genotype (OR = 1.76, 95% CI 1.03-3.00, P = 0.057) in males. CONCLUSIONS: Genetic polymorphisms in ALDH2 modified ischemic stroke risk and outcome in Chinese males, but not in females.

Impact of Tag Single Nucleotide Polymorphisms (SNPs) in CCL11 Gene on Risk of Subtypes of Ischemic Stroke in Xinjiang Han Populations.

BACKGROUND CCL11 is an important inflammatory cytokine associated with inflammation-related diseases such as atherosclerosis and stroke. The aim of this study was to investigate the relationship between CCL11 gene polymorphism with subtypes of ischemic stroke in Xinjiang Han populations. MATERIAL AND METHODS The improved multiple ligase detection reaction (iMLDR) method was used to analyze the genotypes of 6 tag SNPs in the CCL11 gene (rs1129844, rs17809012, rs1860183, rs1860184, rs4795898, and rs4795895) in a case-control study of 406 lacunar stroke patients, 214 large-artery atherosclerotic (LAA) stroke patients, and 425 controls. RESULTS We found the GG genotype of rs4795895 was significantly associated with increased risk of lacunar stroke (adjusted OR=1.676, 95%CI=1.117-2.515), and the GA genotype of rs17809012 was associated with a significant increase in risk of LAA stroke (adjusted OR=1.337, 95%CI=1.127-1.585). Hypertension stratification analyses showed that the GA genotype of rs17809012 was significantly associated with LAA stroke in the hypertensive group (adjusted OR=1.274, 95%CI=1.015-1.601). In the non-hypertensive group, the GA genotype of rs17809012 was significantly associated with LAA stroke (adjusted OR=1.361, 95%CI=1.041-1.780). The GG genotype of rs4795895 (adjusted OR=1.147, 95%CI=1.115-4.134) and the TT genotype of rs1860184 were significantly associated with lacunar stroke (adjusted OR=2.440, 95%CI=1.550-3.840). CONCLUSIONS This study demonstrates that the CCL11 gene could play an important role in the pathogenesis of lacunar stroke and LAA stroke in the Han population of China.

Fine-Mapping of ABO Gene Identifies Two Novel SNPs Associated with Large Artery Atherosclerotic Stroke in a Chinese Han Population.

Recently, a single nucleotide polymorphism (SNP) rs505922 in ABO gene was related to large artery atherosclerotic (LAA) stroke in Caucasian populations by genome-wide association study (GWAS). This study aimed to determine whether ABO gene polymorphisms are associated with LAA stroke in Chinese Han population. A case-control study was designed, and 644 patients with LAA stroke and 642 healthy controls were enrolled. Ten tagging SNPs (tSNPs) located in ABO gene were genotyped. Associations between genotypes and LAA stroke were analyzed with logistic regression model after adjustment of potential confounders. Although rs505922 was not associated with LAA stroke (TT genotype, adjusted OR = 1.32; 95 % CI, 0.94 to 1.87), two novel SNPs, rs8176668 (AT genotype, adjusted OR = 0.71; 95 % CI, 0.55 to 0.92) and rs2073824 (AA genotype, adjusted OR = 0.72; 95 % CI, 0.57 to 0.92), were associated with LAA stroke. Haplotype analysis indicated that haplotype TC (adjusted OR = 0.72; 95 % CI, 0.54 to 0.95; P = 0.018) in block 1 and haplotype ACA in block 2 (OR = 0.73; 95 % CI, 0.58 to 0.91; P = 0.005) were associated with LAA stroke. Multifactor dimensionality reduction (MDR) analysis in the single-locus model indicated that rs2073824 was the most important attributor for predicting risk of LAA stroke. No significant SNP-SNP interactions among the tested SNPs were detected. The results indicated that the genetic variants in ABO gene may influence the risk of LAA stroke in Chinese Han population.

A Novel Functional Polymorphism in the NINJ2 Promoter Predicts Risk of Large Artery Atherosclerotic Stroke.

A recent genome-wide association study (GWAS) identified two common polymorphisms (rs12425791 and rs11833579) on chromosome 12p13 that confer risk to stroke, particularly for large artery atherosclerotic (LAA) stroke. However, these two polymorphisms are located ∼11 kb upstream of the NINJ2 gene and their effects on NINJ2 expression have not been well characterized. Through linkage disequilibrium and fine-mapping analysis, we identified a novel functional polymorphism in the NINJ2 promoter (rs3809263 G > A) and examined its association with risk of LAA stroke in Chinese population. Rs3809263 was genotyped using the improved multiple ligase detection reaction in 414 patients with LAA stroke and 423 healthy controls. A significant decreased risk of LAA stroke was found for the rs3809263 GA (adjusted odd ratio [OR] = 0.63, 95 % confidence interval [CI] = 0.46-0.88) and AA (OR = 0.54, 95 % CI = 0.35-0.84) genotypes. Moreover, genotype-phenotype correlation analysis indicated that the AA genotype carriers had significantly increased NINJ2 mRNA expression levels in the Chinese population, suggesting that the rs3809263 G > A polymorphism is a functional SNP and a biomarker for risk of LAA stroke. Further validation of the functionality of the NINJ2 rs3809263 G > A polymorphism and its association with risk of LAA stroke in other ethnic populations is warranted.

Association of C7673T polymorphism in apolipoprotein B gene with ischemic stroke in the Chinese population: a meta-analysis.

BACKGROUND: Epidemiological studies have evaluated the association between the C7673T polymorphism in apolipoprotein B (apoB) gene and ischemic stroke (IS), but the results are still debatable even in the Chinese population. This meta-analysis was therefore designed to clarify these controversies. METHODS: All of the relevant studies were identified from PubMed, Embase, Chinese National Knowledge Infrastructure database and Chinese Wanfang database up to 31 October 2014. Statistical analyses were conducted with Revman 5.2 and STATA 12.0 software. Odds ratio (OR) with 95% confidence interval (CI) values were applied to evaluate the strength of the association. A fixed or random effect model was selected for pooling data based on the heterogeneity test. Publication bias was assessed by Begg's test and Egger's test. RESULTS: A significant association was found between the C7673T polymorphism in apoB gene and IS under the heterozygous genetic model (OR = 1.868, 95% CI = 1.160-3.007) and the allelic genetic model (OR = 1.742, 95% CI = 1.294-2.346), respectively. In the subgroup analysis by the geographic region, T allele could increase the risk of IS in northern Chinese (OR = 2.359, 95% CI: 1.425-3.907), but not in southern Chinese individuals (OR = 1.485, 95% CI: 0.778-2.832). Further stratification for source of controls showed that statistical significance was found among the population-based studies. CONCLUSION: Our meta-analysis revealed that C7673T polymorphism in apoB gene was significantly associated with increased IS risk in the Chinese population.

[Protective effects of uric acid on nigrostriatal system injury induced by 6-hydroxydopamine in rats].

OBJECTIVE: To investigate the protective effects of uric acid on nigrostriatal system injury induced by 6-hydroxydopamine in rats. METHODS: Thirty male SD rats were divided into four groups. Uric acid of 100 mg/kg, 200 mg/kg, 250 mg/kg were injected intraperitoneally (ip) into 5, 10, 5 rats twice daily at a 2-hour interval for five days and saline was injected ip into 10 rats as controls. At Day 6, 6-hydroxydopamine was injected into striatum to establish Parkinson's disease (PD) model in rats. Then uric acid was injected ip into three groups and saline into controls for five days. Locomotion test, amphetamine-induced rotation and forepaw adjusting step test were performed at Weeks 3 and 4 respectively after injection of 6-hydroxydopamine. HPLC-MS/MS was performed to detect the contents of dopamine and its metabolite homovanillic acid (HVA) in striatum at Week 5. RESULTS: The scores of locomotion in 2 minutes of 200 mg/kg uric acid group (14 +/- 4/2 min) was higher significantly than saline group (4 +/- 5/2 min, P < 0.01). The amphetamine-induced rotation number in the 200 mg/kg uric acid group (10.8 +/- 7.5) was lower significantly that in the saline group (19.3 +/- 5.2, P < 0.01). Forepaw adjusting step test scores of 200 mg/kg uric acid group were higher significantly than those in the saline group (9.89 +/- 3.41 vs 4.36 +/- 3.72, P < 0.01). HPLC-MS/MS showed that the contents of DA (0.29 +/- 0.19) and HVA (1.22 +/- 0.5) in injured striatum of 200 mg/kg uric acid group were higher significantly than those in the saline group (0.05 +/- 0.03, P < 0.01; 0.24 +/- 0.13, P < 0.05). CONCLUSION: An appropriately elevated level of uric acid may protect the dopamine neuron of nigrostriatal system from injury of 6-hydroxydopamine in rats.