Exploring the brain's structural connectome: A quantitative stroke lesion‐dysfunction mapping study

The aim of this work was to quantitatively model cross‐sectional relationships between structural connectome disruptions caused by cerebral infarction and measures of clinical performance. Imaging biomarkers of 41 ischemic stroke patients (72.0 ± 12.0 years, 20 female) were related to their baseline performance in 18 cognitive, physical and daily life activity assessments. Individual estimates of structural connectivity disruption in gray matter regions were computed using the Change in Connectivity (ChaCo) score. ChaCo scores were utilized because they can be calculated using routinely collected clinical magnetic resonance imagings. Partial Least Squares Regression (PLSR) was used to predict various acute impairment and activity measures from ChaCo scores and patient demographics. Statistical methods of cross‐validation, bootstrapping and multiple comparisons correction were implemented to minimize over‐fitting and Type I errors. Multiple linear regression models based on lesion volume and lateralization information were constructed for comparison. All models based on connectivity disruption had lower Akaike Information Criterion and almost all had better goodness‐of‐fit values (R²: 0.26–0.92) than models based on lesion characteristics (R²: 0.06–0.50). Confidence intervals of PLSR coefficients identified brain regions important in predicting each clinical assessment. Appropriate mapping of eloquent functions, that is, language and motor, and replication of results across pathologies provided validation of this method. Models of complex functions provided new insights into brain‐behavior relationships. In addition to the potential applications in prognostication and rehabilitation development, this quantitative approach provides insight into the structural networks underlying complex functions like activities of daily living and cognition. Quantitative analysis of big data will be invaluable in understanding complex brain‐behavior relationships. Hum Brain Mapp 36:2147–2160, 2015. © 2015 Wiley Periodicals, Inc.     

Shared Neuropathological Characteristics of Obesity,Type 2 Diabetes and Alzheimer’s Disease: Impacts on Cognitive Decline

In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer’s disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes.     

养阴行血方对实验性光损伤大鼠视网膜感光细胞的保护作用

目的观察养阴行血方对实验性光损伤视网膜感光细胞的保护作用。方法从实验大鼠80只中随机抽取20只为A组,即空白对照组;其余60只以光照造模。造模后随机分为3组,每组20只,其中B组为模型对照组,C组为杞菊地黄丸治疗对照组,D组为养阴行血方治疗组。治疗2周后随机抽取各组中的10只大鼠处死,取右眼视网膜作光镜观察,取左眼视网膜作透射电镜检查。结果养阴行血方治疗组的光感受细胞内外节分明、胞膜完整、胞核可辨,损伤轻于模型对照与治疗对照纽。结论养血行血方能够减轻光损伤对视网膜感光细胞造成的损害。     

兔肝VX2瘤血供程度对HIFU作用效果影响的初步研究

目的 探讨兔肝VX2瘤实质期血供程度对高能聚焦超声(HIFU)后肿瘤靶点处温度及凝固性坏死体积(V)大小的影响,为进一步精确控制HIFU剂量、提高治疗效率提供实验依据.方法 制作瘤兔24只并分成:10、15、20 d、无血供组(10 d成模后处死)4组,在对应时间进行相同参数HIFU辐照,对靶点实时测温,做出时间-温度曲线(TTC),测量V,对坏死周边残存肿瘤组织及正常肝组织进行微血管密度(MVD)计数.结果 (1)肿瘤MVD:10 d组＞15 d组＞20 d组(P＜0.05).(2)峰值温度(Tmax)、峰值时间(T1)、温升斜率(k1):10 d组、15 d组、20 d组之间比较差异无统计学意义(P＞0.05),此三组与无血供组比较差异有统计学意义(P＜0.05).(3)温降斜率(k2):10 d组＞15d组＞20 d组＞无血供组(P＜0.05);温降时间(T2):10 d组＜15 d组＜20 d组＜无血供组(P＜0.05);(4)V:10 d组＜15 d组＜20 d组＜无血供组(P＜0.05).结论 肿瘤血供程度对HIFU“温升”过程无显著影响,而对“冷却”过程有显著的影响.肿瘤血供越丰富,辐照后散热越快,组织越易恢复到正常温度,形成V越小.     

The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice

AIM:To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE^+/- mice (AChE knockout mice) of various ages.METHODS:Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 μmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE^+/- mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer.RESULTS:Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE^+/- mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE^+/- mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05).CONCLUSION:In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.     

Rat models of cardiometabolic diseases: baseline clinical chemistries,and rationale for their use in examining air pollution health effects

Abstract

Individuals with cardiovascular and metabolic diseases (CVD) are shown to be more susceptible to adverse health effects of pollutants. Rodent models of CVD are used for examining susceptibility variations. CVD models developed by selective inbreeding are shown to represent the etiology of human disease and metabolic dysfunction. The goal of this article was to review the origin and the pathobiological features of rat models of varying CVD with or without metabolic syndrome and healthy laboratory rat strains to allow better interpretation of the data regarding their susceptibility to air pollutant exposures. Age-matched healthy Sprague–Dawley (SD), Wistar (WIS) and Wistar Kyoto (WKY), and CVD-prone spontaneously hypertensive (SH), Fawn-Hooded hypertensive (FHH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF) and insulin-resistant JCR:LA-cp obese (JCR) rat models were considered for this study. The genetics and the underlying pathologies differ between these models. Normalized heart weights correlated with underlying cardiac disease while wide differences exist in the number of white blood cells and platelets within healthy strains and those with CVD. High plasma fibrinogen and low angiotensin converting enzyme activity in FHH might relate to kidney disease and associated hypertension. However, other obese strains with known kidney lesions do not exhibit decreases in ACE activity. The increased activated partial thromboplastin time only in SHSP correlates with their hemorrhagic stroke susceptibility. Increases plasma lipid peroxidation in JCR might reflect their susceptibility to acquire atherosclerosis. These underlying pathologies involving CVD and metabolic dysfunction are critical in interpretation of findings related to susceptibility variations of air pollution health effects.     

冠状动脉再狭窄的动物模型

在冠脉支架应用的时代,再狭窄仍然制约着经皮冠脉介入治疗。许多动物模型被用于研究冠状动脉再狭窄的病理生理机制,并探讨其防治途径。现就近年来冠脉再狭窄动物模型研究的相关进展作一综述。