Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

Fine-tuning of microglia polarization prevents diabetes-associated cerebral atherosclerosis.

Diabetes increases the occurrence and severity of atherosclerosis. When plaques form in brain vessels, cerebral atherosclerosis causes thickness, rigidity, and unstableness of cerebral artery walls, leading to severe complications like stroke and contributing to cognitive impairment. So far, the molecular mechanism underlying cerebral atherosclerosis is not determined. Moreover, effective intervention strategies are lacking. In this study, we showed that polarization of microglia, the resident macrophage in the central nervous system, appeared to play a critical role in the pathological progression of cerebral atherosclerosis. Microglia likely underwent an M2c-like polarization in an environment long exposed to high glucose. Experimental suppression of microglia M2c polarization was achieved through transduction of microglia with an adeno-associated virus (serotype AAV-PHP.B) carrying siRNA for interleukin-10 (IL-10) under the control of a microglia-specific TMEM119 promoter, which significantly attenuated diabetes-associated cerebral atherosclerosis in a mouse model. Thus, our study suggests a novel translational strategy to prevent diabetes-associated cerebral atherosclerosis through in vivo control of microglia polarization.

Association Between Early Cognitive Impairment and Midterm Functional Outcomes Among Chinese Acute Ischemic Stroke Patients: A Longitudinal Study.

Background: Cognitive decline is common after stroke. The influence of early cognitive impairment on midterm functional outcomes among Chinese acute ischemic stroke (AIS) patients has not been fully studied. The aim of the study was to assess the association between early cognitive impairment and midterm functional outcomes among Chinese AIS patients. Methods: A longitudinal survey focusing on Chinese AIS patients was conducted in three stroke centers in Shanghai, China (July to December 2016). A total of 185 eligible patients were interviewed at acute stage and at 1, 3, and 6 months after onset. Patients' functional outcomes were measured by modified Rankin Scale (mRS) and Barthel Index (BI) at each time point. Cognitive function was assessed using Montreal Cognitive Assessment, Changsha version (MoCA-CS), within 7 days after stroke onset. Covariates included patient's demographic characteristics, socioeconomic status, clinical characteristics of stroke, vascular risk factors, receiving rehabilitation after discharge from acute hospital, and recurrence. Generalized linear mixed models and general linear mixed models were applied. Results: The prevalence of cognitive impairment at acute stage of stroke among these patients was 88.1%. The risk of disability (mRS 2-5) of all patients after stroke decreased over time (OR = 0.491, 95% CI = 0.401-0.603). The risk of disability among those with cognitive impairment increased compared with those with normal cognition (OR = 7.384, 95% CI = 1.041-52.407). The BI score of all patients increased over time after controlling for covariates (ß = 1.51, p < 0.01). The BI score of those with cognitive impairment was lower than that with normal cognition over the follow-up period after controlling for other covariates (ß = -8.11, p < 0.05). Conclusions: This study showed that early cognitive impairment was associated with higher risk of disability and poor activity of daily living (ADL) among Chinese AIS patients. Further studies are needed to examine the linkage between multi-domain cognitive impairment and long-term disability and ADL among stroke survivors by using neuropsychological test batteries.