摘要：Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds: hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer's disease(AD). We analyzed by an inverse docking procedure(INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE,PSEN, IDE, CASP, calpain and TNF-a, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aβ deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.

摘要：Scavenging reactive oxygen species(ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury(CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2 O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 couldemerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

摘要：目前应用于阿尔茨海默病(Alzheimer disease,AD)和帕金森病(Parkinson disease,PD)的脑功能成像技术主要包括fMRI、PET等。临床工作中,AD和PD患者对复杂的认知任务很难配合。静息态fMRI具有设计简单、临床易实施、患者易配合等优势,成为AD和PD影像标志物研究中的热点;而基于特异性显像剂的PET检查在提高AD和PD诊断的特异度方面也具有明显优势。在新的脑功能成像技术出现之前,静息态fMRI和PET检查将会是AD和PD脑损伤机制研究的主要手段之一。1 MRI 1.1 AD AD起病隐匿,呈慢性进行性发展。研究[1]发现,从AD临床前期主观认知下降(subjective cognitive decline,SCD),到轻度认知障碍(mild cognitive impairment,MCI),再到AD痴呆期,皆伴随着脑结构与功能异常改变。由于病理导致的功能改变明显早于结构改变,所以如何应用fMRI早期探测AD一直是临床科研工作的焦点。目前针对静息态fMRI数据已经发展和衍生出多种后处理方法,包括基于体素的相关分析、独立成分分析法、图论、低频振幅及局部一致性等。Wang等[2]以手动勾画的双侧海马作为种子点进行基于体素的全脑功能连接分析,结果显示轻度AD患者右侧海马功能连接破坏减弱,提示AD患者默认网络(default mode network,DMN)活性减低;Qi等[3]利用独立成分分析手段发现遗忘型轻度认知障碍(amnestic MCI,aMCI)患者DMN不仅存在特定脑区活性减低,而且可见子网络活性代偿性增高。另有研究[4]提示aMCI患者DMN除有大范围功能障碍外,内部各节点间也存在连接异常,且这种连接异常与患者临床认知评分相关。2017年一项基于静息态功能连接的Meta分析发现[5],aMCI患者DMN长距离及短距离功能连接均发生明显改变,且与临床认知评分密切相关,有望成为评价aMCI的有力指标。本期闫少珍等[6]的报道结果也进一步确认了aMCI患者长短程功能的具体损害方式对于早期诊断aMCI具有重要意义。另外,ASL技术作为一种无创的脑灌注成像手段,可通过脑血流量(cerebral blood flow,CBF)反映脑组织病理改变,而观察脑血流灌注动态变化是随访aMCI的简便有效方法。AD患者的脑功能成像不仅可以较结构成像更早地发现病理改变,而且有助于揭示其认知功能改变的神经生物学机制。

摘要：脑性瘫痪,简称脑瘫(cerebral palsy, CP)是一组持续存在的中枢性运动和姿势发育障碍、活动受限症候群,这种症候群是由于发育中的胎儿或婴幼儿脑部非进行性损伤所致。脑性瘫痪的运动障碍常伴有感觉、知觉、认知、交流和行为障碍,以及癫痫和继发性肌肉、骨骼问题[1]。脑瘫的治疗目标之一是通过综合康复治疗改善患儿运动功能,包括肌力,运动耐力,关节活动度等[2]。神经发育学疗法(neuro developmentaltreatment, NDT)在脑瘫儿童康复治疗中起着非常重要的作用,其基于Bobath 于1940 年设计的一个概念模型,通过刺激运动关键点抑制异常运动模式并促通正常的运动模式,且强调逐渐建立自身调节反应[3—4],旨在最大限度提高儿童运动能力并阻止肌肉骨骼等继发性损伤[5]。目前,NDT广泛应用于脑瘫儿童的康复治疗,且对发育迟缓等有着积极作用[6—7]。随着循证医学在脑瘫儿童康复领域的广泛应用,诸多学者开展了关于脑瘫康复治疗措施的循证分析,现就国内外对NDT 在脑瘫儿童康复治疗中的循证学研究及相关争议问题进行综述。

摘要：新的研究数据表明,直接口服抗凝药可能是脑静脉血栓形成(cerebral venous thrombosis,CVT)抗凝治疗的合适选择。然而,由于该病较为罕见且不良转归事件(如严重出血和功能依赖)发生率低,因此开展高质量的临床试验具有挑战性。为了帮助未来CVT试验的设计,加拿大不列颠哥伦比亚大学的Field等进行了一项Ⅱ期、前瞻性、开放标签、盲法终点试验——SECRET(Study of Rivaroxaban for cerebral Venous Thrombosis),旨在评估:(1)病例招募的可行性;(2)利伐沙班相对于标准抗凝治疗的安全性;(3)以患者为中心的功能转归。