免疫应答异常与中枢神经系统退变性疾病

免疫功能异常参与了中枢神经系统退变性疾病的发生。中枢免疫功能异常主要为小胶质细胞异常激活。激活的小胶质细胞可形成活性中间代谢产物、一氧化氮、促炎因子等细胞毒性物质。发病率最高的两种中枢神经系统退变性疾病阿尔茨海默病（Alzheimer′s disease,AD)和帕鑫森病（Parkinson′s disease,PD)的发生都与免疫功能异常密切相关。由于免疫功能异常特别是小胶质细胞激活普遍存在于中枢神经系统退变性疾病过程中，调节小胶质细胞功能的药物可能会具有神经保护作用，延迟甚至阻止神经元变性。     

生长因子缓释制剂在神经系统退变性疾病中的应用

利用缓释系统包载生长因子,既能保护生长因子的生物活性,又可以使其缓慢释放。从载体材料与生长因子的简单混合到生长因子缓释微球系统,生长因子缓释技术不断更新并得到广泛应用。就生物可降解生长因子缓释制剂在神经系统退变性疾病中的应用做一综述。     

脑源性神经营养因子在异常免疫应答相关神经系统变性疾病中的作用

神经系统变性疾病是一类由成熟神经元进行性变性、坏死所引起认知及行为异常的疾病,严重时会导致患者死亡,目前尚无有效的治疗手段。有研究表明,免疫应答异常普遍存在于中枢神经系统变性疾病过程中,并会导致蛋白质脑源性神经营养因子(BDNF)的减少,引起运动、认知及记忆等障碍。BDNF在神经系统变性疾病中免疫应答异常的作用可能涉及多种机制,虽然目前尚无定论,但BDNF相关的治疗手段,有可能从调节机体免疫能力的角度,为神经系统变性疾病的治疗提供新思路,有着重大的意义。因此,有关BDNF介导的免疫反应在神经系统变性疾病中作用的研究已成为近年来的热点。本文就此进行探讨,并对与BDNF相关的神经系统变性疾病的治疗手段进行综述。     

改良TLIF治疗腰椎退变性疾病

目的探讨改良TLIF治疗腰椎退变性疾病的疗效。方法用改良TLIF手术治疗L3～S1退变性疾病患者24例,共融合40个节段,其中单节段8例,双节段16例。男14例,女10例;年龄56～78岁,平均64.6岁。退变性滑脱伴椎管狭窄6例,峡不连性滑脱4例,退变性腰椎管狭窄症10例,巨大椎间盘脱出合并椎间失稳4例。术中根据病情需要,采用椎管扩大减压后切除整个下关节突,切除上关节突上部的内侧半,部分开放椎间孔后壁,椎间隙自体微粒骨打压植骨,Cage斜向中线40°方向植入椎间隙,辅以椎弓根螺钉固定完成改良TLIF。结果术中无并发症发生,24例均获得随访,时间12～20个月,平均17.4个月。所有患者于术后1年随访时均达椎体间融合,无螺钉断裂和Cage移位、沉陷。10例腰椎滑脱者滑脱完全复位并维持良好。根据JOA评分法,本组术前(13.8±4.1)分,末次随访时(24.9±3.0)分,临床改善程度达优16例,良6例,可2例,平均改善率79.5%。结论改良TLIF扩大了手术适应证,贯彻了TLIF技术的设计思想和微创理念,使操作更加简单、安全,用于下腰椎退变性疾患的治疗效果满意。     

泛素蛋白水解酶体通路与神经系统变性疾病

神经系统变性疾病的一个共同特征就是细胞内与细胞外突变或损害的蛋白异常聚集 ,导致选择性神经元变性与丢失。泛素蛋白水解酶体通路 (UPP)通过泛素依赖的蛋白质水解 ,在处理受损害的和有毒性的蛋白质方面发挥着重要的作用。目前 ,在很多神经系统变性疾病中发现UPP通路受到抑制。     

内固定在退变性腰椎疾病中的应用研究

目的探讨内固定在退变性腰椎疾病的应用研究。方法采用椎弓根内固定系统结合融合治疗退变性腰椎疾病89例，其中后外侧融合63例，后外侧结合Telamon融合器3例，结合Pyramesh融合器23例。结果89例术后随访4～21月，平均12．5月，术后有1例出现假关节内固定松动断裂，8例影像学表现有假关节形成。骨融合率为91．01％。疗效评定按日本骨科学会(JOA)下腰痛评分15分法评定，术前平均3．6分，术后平均13．8分，随访结果采用改善率表示，结果术后平均改善率89．47％。优级改善率75％～100％共55例(80．01％)，良级改善率50％～74％共11例，可级改善率25％～49％2例。全组优良率92．13％。结论在退变性腰椎疾病的治疗中使用内同定，可提高融合率，早期康复。     

内固定在退变性腰椎疾病中的应用研究

目的探讨内固定在退变性腰椎疾病的应用研究.方法采用椎弓根内固定系统结合融合治疗退变性腰椎疾病89例,其中后外侧融合63例,后外侧结合Telamon融合器3例,结合Pyramesh融合器23例.结果89例术后随访4～21月,平均12.5月,术后有1例出现假关节内固定松动断裂,8例影像学表现有假关节形成.骨融合率为91.01%.疗效评定按日本骨科学会(JOA)下腰痛评分15分法评定,术前平均3.6分,术后平均1 3.8分,随访结果采用改善率表示,结果术后平均改善率89.4 7%.优级改善率75%～100%共55例(80.01%),良级改善率50%～74%共11例,可级改善率25%～49%2例.全组优良率92.13%.结论在退变性腰椎疾病的治疗中使用内固定,可提高融合率,早期康复.     

棘突间稳定器在腰椎间盘退变性疾病中的初步应用

目的分析棘突间稳定器治疗腰椎间盘退变性疾病的初步临床效果。方法 2009年6月～2009年12月,应用棘突间稳定器治疗腰椎间盘退变性疾病31例,其中男12例,女19例,年龄平均53.5岁（31～74岁）。对所有患者平均随访7个月（4～10个月）,分别于术前、术后3个月行下腰痛JOA评分,并拍X线片复查。结果手术时间平均65分钟（45～90分钟）,安放棘突间稳定器系统的时间为10～15分钟,术中出血50ml-300ml。下腰痛JOA评分与术前相比较有明显统计学差异（术前为12.84±3.65,术后3个月为20.55±3.41,P〈0.01）。未出现棘突间稳定器移位、松动、棘突骨折、腰椎后凸畸形等并发症。结论棘突间稳定器是治疗腰椎间盘退变性疾病的一种安全、有效的手术方法 ,其远期效果有待进一步观察。     

神经系统疾病的基因治疗

很可能不久在许多中枢神经系统疾病和损伤的治疗中建立起遗传学治疗方法。这类治疗的对象不仅包括致病基因，而且还包括神经生长因子（神经生长因子影响神经元的存在和功能）和异常的继发代谢及神经传导功能。     

直视法植入螺钉在腰椎退变性疾病椎弓根螺钉固定的应用

目的　探讨直视法植入螺钉在腰椎退变性疾病椎弓根螺钉固定的应用效果。 方法　120例腰椎退变性疾病行后路切开椎弓根螺钉内固定治疗患者。按螺钉植入方式不同,分为以人字嵴为解剖标志的传统法组（A组,80例）和椎板切除或开窗后直视下以椎弓根内下缘为解剖标志的直视法组（B组,40例）。两组患者性别、年龄、病种、病程等一般资料比较,差异无统计学意义（P>0.05）。比较两组植入螺钉的透视时间、植入螺钉时间、术中出血量、融合率、功能恢复（JOA评定法）和并发症情况。 结果　B组的透视时间、植入螺钉时间和术中出血量小于A组,螺钉位置好于A组,差异有统计学意义（P<0.05）;B组的功能恢复和并发症好于A组,但差异无统计学意义（P>0.05）;两组融合率均100%。 结论　直视法植入椎弓根螺钉方法简单、效果良好,可以作为腰椎退变性疾病某些情况下传统法的一种补充。     

神经营养因子与神经元退行性变疾病

神经元退行性变疾病包括多种疾病,如常见的老年性痴呆（alzheimer’s disease,AD）和帕金森病（parkinson disease,PD）等。此类疾病的共同特点是进行性的神经元损伤。由于发病机制复杂,并涉及许多至今未知的因素,目前尚无有效的干预措施,故阐明神经元退行性变疾病的发生机制十分重要。神经营养因子（neurotrophic factors,NTFs）是一类调节神经系统发育、成熟和维持神经元功能的天然蛋白质,在神经系统的发生、发育、营养、存活及损伤后修复中起重要作用,是神经元存活和发挥功能的基础。因此,本文主要讨论NTFs与神经元退行性变疾病特别是AD和PD之间的关系。     

Circular RNAs: emerging players in brain aging and neurodegenerative diseases

Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.     

MicroRNAs (miRNAs) in neurodegenerative diseases

Aging-related neurodegenerative diseases (NDs) are the culmination of many different genetic and environmental influences. Prior studies have shown that RNAs are pathologically altered during the inexorable course of some NDs. Recent evidence suggests that microRNAs (miRNAs) may be a contributing factor in neurodegeneration. miRNAs are brain-enriched, small ( approximately 22 nucleotides) non-coding RNAs that participate in mRNA translational regulation. Although discovered in the framework of worm development, miRNAs are now appreciated to play a dynamic role in many mammalian brain-related biochemical pathways, including neuroplasticity and stress responses. Research about miRNAs in the context of neurodegeneration is accumulating rapidly, and the goal of this review is to provide perspective for these new data that may be helpful to specialists in either field. An overview is provided about the normal functions for miRNAs, including some of the newer concepts related to the human brain. Recently published studies pertaining to the roles of miRNAs in NDs--including Alzheimer's disease, Parkinson's disease and triplet repeat disorders-are described. Finally, a discussion is included with theoretical syntheses and possible future directions in exploring the nexus between miRNA and ND research.     

深部脑刺激治疗帕金森病疗效分析

目的研究深部脑刺激（deep brain stimulation，DBS）对帕金森病（Parkinson’s disease，PD）的治疗作用，探讨DBS对PD震颤、肌僵直、运动缓慢的疗效及术中靶点的确定。方法采用微电极记录下丘脑底核（STN）和丘脑腹中间核（Vim）慢性电刺激术对4例PD患者进行治疗。其中3例DBS于STN、1例DBS于Vim。结果3例STN术中刺激发现，能改善PD的震颤、僵直、运动缓慢等主要症状；1例Vim术中刺激发现，患者的震颤和运动缓慢得以改善。4例PD患者经过1～3次的调试，4～6年的随访发现，患者的主要症状改善情况不如短期疗效，但仍较术前有较大改善，通过调节程控参数，可以达到满意。其运动部分（UPDRS）评分，术后改善率43％～48％之间。1例合并上肢疼痛患者经3次调试疼痛症状改善不明显，2年后取出埋藏电极。4例患者均没有出现永久性并发症。结论STN的DBS能改善PD的震颤、僵直、运动缓慢等主要症状；Vim的DBS能改善PD的震颤和运动缓慢。DBS是治疗PD双侧症状的优选方法，其可逆性对患者有较高的安全性。     

The endocannabinoid pathway in Huntington's disease: a comparison with other neurodegenerative diseases

Endocannabinoids are endogenous agonists of cannabinoid receptors, and comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the best-studied members of this class of lipid mediators, and it is now widely accepted that their in vivo concentration and biological activity are largely dependent on a “metabolic control.” Therefore, the proteins that synthesize, transport and degrade endocannabinoids, and that together with the target receptors form the so-called “endocannabinoid system,” are the focus of intense research. This new system will be presented in this review, in order to put in a better perspective the impact of its modulation on Huntington's disease. In particular, the effect of agonists/antagonists of endocannabinoid receptors, or of inhibitors of endocannabinoid metabolism, will be discussed in the context of onset and progression of Huntington's disease, and will be compared with other neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, and amyotropic lateral sclerosis. Also the plastic changes of endocannabinoids in multiple sclerosis will be reviewed, as a paradigm of their impact in neuroinflammatory disorders.     

Characterization of brain samples in studies of aging, Alzheimer''s, and other neurodegenerative diseases

We review current understanding of the clinical and pathologic information needed for the determination of optimal brain tissue samples for the conduct of studies of Alzheimer's disease (AD). Characteristics that may distinguish AD from other dementing disorders are discussed. Selected considerations in the conduct of basic neurobiological studies are also outlined. Although the 28 NIA-funded Alzheimer's Centers can provide excellent clinical and neuropathological data, studies conducted outside these centers should also strive to gather the information suggested here. Clinical and neuropathological data should be used not only to classify subjects as control or AD, but also as variables that may significantly contribute to the analysis of neurobiological data obtained in the laboratory.     

Brain tissue microarrays in neurodegenerative diseases: validation of methodology and immunohistochemical study of growth-associated protein-43 and calretinin

A tissue microarray (TMA) was constructed using 47 neurodegenerative diseases (NDD), including Alzheimer's disease (AD; n = 30) and non-AD NDD (n = 17), and from seven controls. For validation of the methodology, the following three immunostains were used. Tau and beta-amyloid-related pathologies were more significantly recognized in tauopathies/AD compared to non-tauopathies/controls, and these results were comparable to the assessment of the whole brain sections. But no alpha-synuclein pathologies were observed despite five cases of dementia with Lewy bodies. It was concluded that the TMA technique is useful for NDD with diffuse pathological processes but not for those with patchy and occasional lesions or in early stages. Growth-associated protein (GAP)-43 and calretinin were also immunostained. A significant reduction in GAP-43 expression was seen in the frontal lobe and hippocampus in AD compared to non-AD cases, but not in other areas. No significant difference in number of anticalretinin immunoreactive neurons or in density of immunoreactive neurites was observed between any of the NDD and controls, which may indicate that calretinin-positive neurons are spared in the degenerative process. These results are compatible with the previous studies. These analyses were performed rapidly in a large number of cases using a single slide under uniform staining conditions.     

Post mortem sampling of the brain and other tissues in neurodegenerative disease

The importance of the autopsy in neurodegenerative disease is often not appreciated. Yet clinical diagnosis of neurodegenerative disease is relatively inaccurate, many neurodegenerative diseases are inherited or are associated with specific genetic risk factors, and several non-transmissible neurodegenerative diseases may be confused clinically with prion diseases. In all these cases, the autopsy is the only practical way in which brain tissue can be obtained for diagnosis. The pathologist should ensure that consent by the next-of-kin to post mortem examination is based on clear information as to the nature, scope and limitations of the autopsy, and that any constraints on retaining brain and other tissues are documented. The autopsy should be preceded by a careful review of the clinical notes and ante mortem studies, and consideration of the possible and likely pathological processes. This may suggest the need to retain fixed or frozen samples of cerebrospinal fluid, skeletal muscle, peripheral nerve and other tissues in addition to brain and spinal cord. Ideally, the brain should be fixed intact for 2-3 weeks before it is sliced and blocks are taken. If the period of fixation is limited to a few days only, it is best to slice the brain whilst it is fresh and to allow the diagnostically relevant slices to fix flat; after about 3 days the fixed slices can be sliced further, examined macroscopically and sampled. Even if consent is limited to the retention of only a few tissue samples for histology, a reasonably confident diagnosis can still usually be made, provided that the sampling is careful and systematic. The selection of blocks or brain and spinal cord for histology should be based on internationally accepted guidelines for the pathological diagnosis of different types of neurodegenerative disease, where such guidelines are available. Illustrations are provided to indicate which regions of the brain are critical to establishing a diagnosis in the main categories of neurodegenerative disease. When difficulties arise in the pathological diagnosis of neurodegenerative disease, inadequate post mortem sampling or rapid processing of poorly fixed brain tissue is usually to blame.