干细胞治疗神经退行性疾病的前景与问题

背景：虽然各种神经退行性疾病的人群发病率居高不下且有上升趋势,但至今仍无有效治疗方法,因此,寻求有效的治疗神经退行性疾病的途径是科学界面临的挑战.目的：文章分析和综述了对干细胞治疗神经退行性疾病的近年研究进展及热点问题.方法：文章对干细胞移植治疗神经退行性疾病,如阿尔茨海默病、帕金森病、脑卒中、亨廷顿病、视网膜色素变性疾病、肌萎缩性侧索硬化症、癫痫等疾病的基础与临床研究进展进行概述,探讨干细胞治疗神经退行性疾病的可行性、优势及问题.结果与结论：干细胞治疗神经退行性疾病大部分研究还是集中在实验动物模型阶段,还没有支持干细胞临床治疗的有效证据,其安全性和有效性还没有确切临床保证和标准,临床治疗效果及不良反应都有待大宗及长期临床试验研究进一步验证.     

重复经颅磁刺激治疗神经源性膀胱的研究进展

神经源性膀胱(neurogenic bladder, NB)是一种难治性疾病,其特征是膀胱及尿道功能障碍。重复经颅磁刺激(repetitive transcranial magnetic stimulation, rTMS)作为治疗NB的新方法,已被应用于临床并取得一定效果。文章对rTMS在帕金森、多发性硬化、膀胱疼痛综合征、脊髓损伤疾病继发NB中的治疗进行分析归纳。但由于rTMS应用指南缺少对NB治疗的指导性意见,使得其治疗方案不尽相同,且缺失高质量随机对照研究文献,故难以判断治疗方案的优劣。期待高质量的随机对照试验且同质化的rTMS治疗处方,以进一步确认rTMS在NB治疗中的有效性,并规范NB的临床治疗。     

非侵入性脑部刺激技术改善认知障碍的研究进展

非侵入性脑部刺激技术(NIBS)作为一种安全、新型的治疗技术,在改善脑卒中、帕金森病、阿尔茨海默病等器质性或非器质性疾病引起的认知功能障碍中均显示出较好的应用前景。近年来重复经颅磁刺激(rTMS)临床应用和临床研究较多,改善认知功能障碍效果相对明确,经颅直流电刺激(tDCS)与经颅交流电刺激(tACS)的应用研究也展现出较大的潜力。三者无论是单独治疗或联合治疗均显示出可改善认知功能的效果。其治疗模式选择、参数设置、联合治疗方案是治疗效果的关键要素,需要个体化治疗设计。本文结合三者改善认知功能的作用机制、临床效果、刺激参数、新型刺激模式、安全性等进行综合分析与比较,展望其未来的临床应用前景。     

重复经颅磁刺激辅助治疗抑郁症

重复经颅磁刺激（repetitive transcranial magneti cstimulation,rTMS）是近年兴起的一种物理疗法，但其在神经、精神学科领域的临床应用还未被广为认同。抑郁症是一种常见的情感障碍性精神病。国外有文献报导，rTMS能兴奋大脑皮层中水平走向的联结神经元，并可使大脑皮层局部代谢水平增高，在治疗抑郁症方面显示了巨大的应用潜力。本研究旨在探讨rTMS辅助治疗抑郁症的疗效，报道如下。     

重复经颅磁刺激在康复科常见疼痛中的临床应用

重复经颅磁刺激（rTMS）作为一种无创安全的治疗方法,逐渐被应用于精神心理领域、神经康复及疼痛康复领域。而慢性疼痛在康复科很常见,药物治疗效果不佳,越来越多的研究证实rTMS对慢性疼痛有效。本文对该技术治疗慢性疼痛的研究现状及治疗参数作一综述,以期为临床工作提供参考。     

小脑重复经颅磁刺激对卒中后吞咽障碍的影响及相关机制研究进展

小脑是全脑神经元最密集的部位。近年来有多项研究显示小脑在吞咽活动中发挥重要作用, 与大脑吞咽中枢具有紧密联系, 小脑重复经颅磁刺激(rTMS)对卒中后吞咽障碍恢复具有促进作用。本文旨在介绍小脑调控吞咽的相关神经通路及功能基础, 并探讨小脑rTMS干预卒中后吞咽障碍的作用机制, 为进一步深入研究该领域提供参考资料。     

慢性盆腔疼痛综合征的神经调控治疗进展

慢性盆腔痛综合征(chronic pelvic pain syndrome,CPPS)是临床常见的疼痛性疾病。由于病因复杂,药物、神经阻滞和手术等常规治疗方法往往效果不佳。近年来发现,神经调控(neuromodulation)对CPPS具有较好的治疗作用。目前用于治疗CPPS的神经调控方式主要有骶神经电刺激、阴部神经电刺激、脊髓电刺激、经皮胫神经电刺激和经会阴电磁刺激等。这些神经调控技术的应用,为一些常规方法治疗无效的CPPS患者带来了一种新的治疗方式并有较好的临床疗效。然而神经调控并非使所有CPPS患者均能获益,主要表现在不同的患者、不同的神经调控方式,其镇痛效果有很大不同。但随着对CPPS形成机制和神经调控机理的深入认识,以及神经调控设备和技术的不断进步,神经调控用于CPPS的治疗具有更为广阔的前景。     

重复经颅磁刺激治疗缺血性脑卒中作用机制的研究进展

缺血性脑卒中是因脑动脉狭窄或闭塞导致局部脑组织缺血、缺氧的神经细胞死亡的一类临床综合征,因缺血时间不同出现缺血中心区细胞坏死和缺血半暗带区的细胞凋亡。重复经颅磁刺激（rTMS）是一种新型无创、无痛的绿色疗法,其磁场刺激可有效穿透颅骨引起大脑皮质电信号的改变。研究发现,寻求rTMS针对缺血半暗带抑细胞凋亡和促缺血区神经可塑性具有重要意义。本文对近年来rTMS治疗缺血性脑卒中机制的相关研究进行了综述,旨在阐明rTMS抗神经细胞凋亡和促神经可塑性的作用机制。     

昼夜节律紊乱与神经退行性变性疾病相关性的研究进展

神经退行性变性疾病是一类以神经元退行性变性、丢失为主的慢性进行性神经系统疾病,包括阿尔茨海默病、帕金森病、亨廷顿舞蹈病和多系统萎缩等。尽管这些疾病发病机制和典型表现不同,但都出现昼夜节律紊乱。昼夜节律是生物体存在的24 h节律,参与调控机体生理过程,昼夜节律紊乱会导致激素分泌异常、致病蛋白积累和神经退行性改变,加速疾病进展。本文对昼夜节律紊乱与神经退行性变性疾病的相关性进行论述。     

葛根素片添加治疗帕金森病患者的疗效观察

帕金森病（Parkinson’s disease,PD）是中老年人群常见的神经退行性疾病。现行的药物治疗只能缓解PD症状并不能彻底治愈或阻止疾病的发展。因此,中西医结合干预PD的发生、发展是一个研究方向。作者应用葛根素片联合美多巴治疗药效减退的帕金森病患者,收到较好的临床疗效,结果报道如下。     

Chronic Respiratory Diseases and Neurodegenerative Disorders: A Primer for the Practicing Clinician

Chronic respiratory disorders represent a world epidemic. Their incidence and prevalence in the world population is increasing, and especially among elderly subjects, they are commonly associated with other pathologies, often generating a status of high clinical complexity. Neurology, internal medicine, and pneumology specialists should be aware of the common background of these disorders in order to treat correctly the patient''s comorbid state and optimize the treatment considering potential overlaps. In this review, we aimed to focus on the relationships between chronic respiratory disorders and chronic neurodegenerative diseases at different levels; we review the shared risk factors and the interactions between disorders, the indications to explore respiratory function in neurodegenerative diseases, pathology-pathology and drug-pathology interactions in patients affected by both chronic neurologic and respiratory diseases.     

Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases

Following the discovery of the human kinome, protein kinases have become the second most important group of drug targets as they can be modulated by small ligand molecules. Moreover, orally active protein kinase inhibitors have recently reached the market and there are many more in clinical trials. The lack of treatments for neurodegenerative diseases has increased human and financial efforts in the search for new therapeutic targets that could provide new effective drug candidates. The importance of kinases in the molecular pathway of neuronal survival is under study, but different key pathways have been described. New roles for the old casein kinases 1 and 2, currently known as protein kinases CK1 and CK2, have recently been discovered in the molecular pathology of different neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis. The search for specific inhibitors of these enzymes has become an important challenge for the treatment of these devastating diseases. The role of these two kinases in the molecular pathology of different neurodegenerative diseases together with different chemical families that are able to more or less specifically inhibit CK1 and CK2 are discussed in this review. © 2010 Wiley Periodicals, Inc. Med Res Rev 31:924‐954, 2011     

Inflammation and aging: Can endocannabinoids help?

Aging often leads to cognitive decline due to neurodegenerative process in the brain. As people live longer, there exists a growing concern linked to long-term, slowly debilitating diseases, such as Alzheimer's disease for which a cure has not yet been found. Recently, the role of neuroinflammation has attracted attention due to its slow onset, chronic nature and its possible role in the development of many different neurodegenerative diseases. In the future, treatment of chronic neuroinflammation may help counteract aspects of neurodegenerative disease. Our recent studies have focused upon the endocannabinoid system for its unique effects on the expression of neuroinflammation. The basis for the manipulation of the endocannabinoid system in the brain in combination with existing treatments for Alzheimer's disease will be discussed in this review.     

睡眠节律紊乱与阿尔兹海默病研究进展

认知功能损害患者睡眠障碍患病率高,表现形式多样,主要包括：失眠、日间过度思睡、睡眠呼吸障碍、异态睡、不宁腿综合征、睡眠节律紊乱等。阿尔茨海默病(Alzheimer"s disease,AD)是最常见的认知损害类型,73%的中国汉族AD患者伴有睡眠障碍,其中53%伴有不同程度的睡眠节律紊乱。AD患者睡眠障碍在病程中后期较为突出,所以一直以来睡眠节律紊乱都被认为是AD相关神经退行性变的结果,例如“日落现象”,患者一到傍晚就焦虑不安、难以入睡,而白天则睡眠过多。但近期研究表明,睡眠节律紊乱很可能参与AD发生的始动环节。国外前瞻性的随访研究发现,睡眠节律紊乱的认知正常老年人群,在5-10年后更容易发生AD。目前,关于睡眠节律紊乱究竟通过何种途径促使神经系统退行性变发生的研究尚不深入,本文将回顾睡眠节律紊乱引发AD相关病理、生物标记物变化的研究报道。     

经颅超声在帕金森病诊断和鉴别诊断中的应用进展

帕金森病（Parkinson''s disease,PD）是临床常见神经变性病,经颅超声(Transcranial sonography,TCS)发现黑质异常高回声(Substantia nigra,SN+)是PD诊断和鉴别诊断的重要辅助检查。但SN+出现的原因不甚清楚,其与症状严重程度的相关性仍有较大争议,与临床分型及分期方面的关系未有定论,TCS亦可通过对中脑中缝和基底节区的探查,提示几种运动及情感障碍的鉴别,越来越多的研究正在不断拓宽TCS在临床实践中的使用。     

Clinical pharmacology of anti-Alzheimer drugs

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and functional abilities, associated with various degrees of behavioural disturbances, with a devastating impact on public health and on the whole society. Slowing of cognitive impairment, duration of disease, self-sufficiency and behavioural disturbances represent the best outcomes of the pharmacologic therapy. Cholinesterase inhibitors (ChE-I) have been shown to be effective in the treatment of the cognitive, behavioural, and functional deficits of AD. In addition to ChE-I, a number of studies have been carried out to investigate the possible use of other compounds and pharmacologic strategies; more compounds, postsynaptic muscarinic and nicotinic receptor agonists, are under investigation. The standard suggested care for pharmacologic management of the cognitive and functional disabilities of AD at present consists of treatment with ChE-I. Practice recommendations and treatment guidelines are derived from clinical trials.     

Histone deacetylases as targets for the treatment of neurodegenerative disorders: Challenges and future opportunities

Despite the applicability of histone deacetylase inhibitors (HDACis) for cancer treatment, several works in the literature have shown that these inhibitors can be used in several other diseases, such as neurodegenerative diseases (NDs). This review begins by discussing the signaling pathways of HDACs, focused on the context of NDs, presenting a discussion about the pharmacophoric features of HDACis and crystal structure analysis and discussing interesting case studies from the literature about the development of HDACis. Additionally, a discussion about the consequences of isoform-selective inhibition vs pan-HDACis on neurotoxic effects and clinical trial investigations of HDACis for NDs is also presented. Finally, we describe our perspective related to the future use of these inhibitors in the pharmacotherapy of NDs.     

Animal Models of Neurodegenerative Disease: Insights from <Emphasis Type="Italic">In vivo</Emphasis> Imaging Studies

Animal models have been used extensively to understand the etiology and pathophysiology of human neurodegenerative diseases, and are an essential component in the development of therapeutic interventions for these disorders. In recent years, technical advances in imaging modalities such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have allowed the use of these techniques for the evaluation of functional, neurochemical, and anatomical changes in the brains of animals. Combining animal models of neurodegenerative disorders with neuroimaging provides a powerful tool to follow the disease process, to examine compensatory mechanisms, and to investigate the effects of potential treatments preclinically to derive knowledge that will ultimately inform our clinical decisions. This article reviews the literature on the use of PET and MRI in animal models of Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease, and evaluates the strengths and limitations of brain imaging in animal models of neurodegenerative diseases.