补体与脑血管疾病

脑血管疾病的发病机制和病理生理过程相当复杂。近年来的研究表明,补体在脑血管疾病的发生发展中有重要作用。脑组织自身可合成补体,脑组织损伤时脑内补体激活,导致一系列损伤。本文就脑内补体的来源、激活、损伤机制及其与脑血管疾病的关系作一综述。     

隐匿性脑血管畸形

本文分析了１２例经手术后病理证实的隐匿性脑血管畸形，对其疾病的发生机理进行了详细讨论。阐述了ＣＴ，ＭＲＩ在此疾病中的特征性表现，结合临床经验探讨了对其手术治疗的意义及重点。     

脑血管支架置入的影响因素及其并发症

目的：针对脑血管支架在脑血管疾病治疗方面的应用，探讨脑血管支架置入的影响因素及其并发症情况。 方法：用计算机检索中国期刊全文数据库(CNKI：1989/2009)和Medline database(1989/2009)，按纳入和排除标准，对文献进行筛选，资料收集和质量评价，共纳入21篇文章。从脑血管支架的临床应用、脑血管支架治疗过程中的影响因素及其在临床治疗过程中的并发症类型与应对方法3方面进行总结。 结果：脑血管支架在临床治疗脑血管方面疾病效果明显，脑血管支架的生物相容性、机体的凝血反应及血流动力学变化等都影响脑血管支架治疗脑血管方面疾病的效果。脑血管支架置入后可能造成的并发症，会对患者造成严重影响，应对其进行有效的预防和处理。 结论：目前在脑血管疾病的治疗中，脑血管支架置入技术发挥着重要作用。但随着支架置入治疗脑血管狭窄的日益增多，发现脑血管支架置入技术仍然很多方面因素的影响，其引起各种并发症逐渐被人们重视。     

脂肪保护性因子与缺血性脑血管病的研究进展

<正>缺血性脑血管病(ischemic cerebrovascular disease,ICVD)具有高致残率及高死亡率特点,其发生与多种危险因素相关,包括高血压、代谢综合征(metabolic syndrome,MS)、感染及高同型半胱氨酸血症等。脑血管疾病的病因及病理机制深入研究,给脑血管病提供了更多的治疗靶点。脂肪因子的发现对缺血性脑血管疾病的病因、病理机制及治疗具有     

蛛网膜下腔出血活体动物模型的研究进展

动脉瘤性蛛网膜下腔出血是一种危害性极强的出血性脑血管疾病，其主要危害是引起继发性脑血管痉挛，机制至今尚未明了。蛛网膜下腔出血活体动物模型在研究脑血管痉挛的病理生理变化及指导临床治疗等方面起到了重要作用。本文对包括鼠、狗、猴、兔在内的活体动物模型研究进展进行综述。     

脑血管支架种类及材料学特点与支架置入后的补体反应

目的：探讨脑血管支架材料学特点及补体反应与支架置入后并发症的关系。 方法：以“脑血管支架，生物材料，生物相容性，再狭窄，补体反应”为中文检索词；以“rebrovascular disease，stent，therapy，complement”为英文检索词，采用计算机检索Pubmed数据库(http://www.ncbi.nlm.nih.gov/PubMed)及维普数据库(http://www.cqvip.com/)2000-01/2008-12有关脑血管支架材料学特点与支架置入后补体反应的文章；排除重复研究及Meta分析类文章。以24篇文献为主重点探讨了脑血管支架材料学特点及补体反应与支架置入后并发症的关系。 结果：金属支架的生物相容性较差，聚合物支架、涂层支架和药物支架的生物相容性较好。脑血管支架作为治疗颅内外血管性疾病的一个重要手段，可降低颅内外动脉狭窄患者缺血性脑卒中的风险，但支架置入后的并发症如再狭窄等问题严重阻碍着该技术的进一步发展，免疫炎症反应在缺血性脑损伤机制中起着重要作用，生物材料对补体系统也有明显的影响。 结论：选用合适的生物医用材料，脑血管支架置入治疗可明显降低脑血管病的死亡率。但要注意脑血管支架置入过程中以及置入后可能发生的并发症，给予积极的防治是非常重要的。研制新的生物医用材料，同时检测补体系统相关指标，将会提高脑血管支架置入治疗的成功率。 关键词：脑血管支架；生物材料；生物相容性；再狭窄；补体反应 doi:10.3969/j.issn.1673-8225.2010.29.031     

信号转导及转录激活因子1与缺血性脑血管疾病的研究进展

目前关于缺血性脑血管疾病发病机制及发病后损伤机制研究尚未完全清楚,信号转导及转录激活因子1(STAT1)属于具有信号转导和转录调节功能的蛋白质家族,近年来诸多研究表明STAT1参与缺血性脑血管疾病的病理过程及损伤机制,目前认为其主要参与了脑缺血后的细胞凋亡、氧化应激等,深入研究以上病理生理过程及损伤机制,将为寻找到有效的治疗药物奠定基础.现将对此综合国内外文献进行综述.     

脑血管疾病患者的支架置入与康复治疗

目的：探讨脑血管支架在治疗脑血管疾病的应用现状,以及脑血管支架置入者的康复治疗对疾病恢复的作用。 方法：用计算机检索中国期刊全文数据库(CNKI：1989/2009)和Medline database(1989/2009),按纳入和排除标准,对文献进行筛选,资料收集和质量评价,共纳入39篇文章。从脑血管支架的应用现状、脑血管支架置入的主要影响因素及主要并发症和脑血管支架置入患者的康复治疗的发展趋势3方面进行总结。 结果：支架置入治疗脑血管疾病较为有效,但支架的材质、技术参数、体内细胞因子等多种因素均可能影响支架置入的效果,且脑血管支架置入引起的各种并发症如血栓形成、脑出血、再狭窄以及高灌注、低灌注等问题仍阻碍着该技术的进一步发展。脑血管疾病支架治疗患者经过康复治疗后其运动功能和生活自理能力得到了改善和提高。 结论：脑血管支架置入虽受到多方面影响,但是以其特有的优势在脑血管疾病治疗方面发展迅速。对脑血管疾病支架置入治疗患者的康复治疗可以最大限度恢复其生活自理能力。     

脑供血不足的病理生理与临床

<正> 脑血管性疾病是危害人类健康的主要疾病之一,在脑血管性疾病当中又以缺血性血管疾病最为常见,深入了解缺血性脑血管疾病的病理生理基础过程及其临床表现是正确预防和治疗脑血管性疾病的前提。根据脑缺血发生的原因不同可以分为脑血栓形成.脑栓塞及血液动力学障碍引起的脑缺血。根据脑缺血的严重程度可分为完全性脑缺血和不完全性脑缺血(脑供     

交感神经在脑血管疾病中作用机制的研究

交感神经在脑血管中分布广泛,生理状态下对脑血管收缩扩张及脑血流量的调节等具有重要作用。在一些病理状态下,如脑血管疾病及脑外伤应激中,交感神经过度收缩脑血管及其递质过度释放会导致脑损伤。而交感神经阻滞及神经递质受体封闭对此类疾病有一定的疗效。本研究回顾脑血管交感神经系统的分布及其生理、病理作用,分析相关递质和介导因子,并对其在脑出血、脑缺血和脑外伤等中的作用和机制做一综述。     

Evidence for activation of the complement cascade in the hypoglossal nucleus following peripheral nerve injury

Following hypoglossal nerve transection in adult rats, immunoreactivity for complement factor C3 and one of its degradation products C3d as well as C4d and immunoglobulin G (IgG) was observed in the ipsilateral hypoglossal nucleus. Double-labelling experiments indicated that these antigens were present in perineuronally located reactive microglial cells. In addition, increased levels of complement factor C3-mRNA was found in perineuronally located cells ipsilateral to nerve lesion. These results suggest that the complement cascade is locally activated in the vicinity of axotomized neuronal perikarya and that microglial cells have a key role in this process, alternatively that C3, C3d, C4d and IgG are involved in other so far unknown processes.     

The Role of the Complement System in Chronic Inflammatory Demyelinating Polyneuropathy: Implications for Complement-Targeted Therapies

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common, heterogeneous, immune-mediated neuropathy, characterized by predominant demyelination of motor and sensory nerves. CIDP follows a relapsing–remitting or a progressive course and causes substantial disability. The pathogenesis of CIDP involves a complex interplay of multiple aberrant immune responses, creating a pro-inflammatory environment, subsequently inflicting damage on the myelin sheath. Though the exact triggers are unclear, diverse immune mechanisms encompassing cellular and humoral pathways are implicated. The complement system appears to play a role in promoting macrophage-mediated demyelination. Complement deposition in sural nerve biopsies, as well as signs of increased complement activation in serum and CSF of patients with CIDP, suggest complement involvement in CIDP pathogenesis. Here, we present a comprehensive overview of the preclinical and clinical evidence supporting the potential role of the complement system in CIDP. This understanding furnishes a strong rationale for targeting the complement system to develop new therapies that could serve the unmet needs of patients affected by CIDP, particularly in those refractory to standard therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01221-y.     

Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells

In this report, we show that in the human astroglioma cell line D54-MG, both interleukin-1 (IL-1β) and tumor necrosis factor-alpha (TNF-α) enhance C3 gene expression in a time- and dose-dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30-fold and 20-fold in response to IL-1β or TNF-α, respectively. C3 protein production increases proportionally, reaching levels 36-fold and 18-fold higher than untreated controls upon exposure to IL-1β or TNF-α, respectively. D54-MG cells require a minimal 1 h exposure to IL-1β in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF-α. Simultaneous treatment of D54-MG cells with IL-1β and interferon-gamma (IFN-γ) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF-α and IFN-γ. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL-1β (5.3-fold increase) and TNF-α (7-fold increase), while an additive effect was observed upon simultaneous treatment with both IL-1β and IFN-γ. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN-γ, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis.     

免疫吸附治疗急性吉兰巴雷综合征

目的观察免疫吸附对急性吉兰巴雷综合征的治疗效果.方法对56例急性吉兰巴雷综合征患者分别进行免疫吸附(Immunoadsorption,IA)治疗及常规治疗,治疗前后观察神经功能改善状况,检测治疗前后血液中免疫系列、补体系列及总蛋白.结果 IA组1月后MRC评分与常规治疗组相比有显著性差异,在半年后Hughes评分两组间的差异有显著意义,治疗后血液中的免疫球蛋白IgG、IgA及补体C3水平明显低于常规治疗组,总蛋白无明显变化.结论 IA是治疗急性吉兰巴雷综合征较为有效的方法,可明显地改善神经功能缺损状况,这可能与降低血液中免疫球蛋白及补体有关.     

Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease

We compared lesions in elderly transgenic (tg) mice carrying the Swedish double mutation KM670/671NL with lesions in Alzheimer disease (AD) by histochemical and immunohistochemical techniques. Highly similar staining for beta-amyloid protein (Abeta) was observed in AD and the mouse models. The abundant amyloid deposits in tg mice were in a consolidated state as revealed by strong Congo red birefringence. In both tg mice and AD, amyloid deposits were ApoE-positive and were surrounded by activated astrocytes. However, Bielschowsky silver staining and immunostaining with tau antibodies revealed no neurofibrillary tangles (NFTs) in the mice as opposed to abundant NFTs in AD. The microglial pattern was also distinctly different. Tg mice had only weakly activated microglia, which expressed low levels of the complement receptor CD11b. They were gathered around the periphery of the deposits. In contrast, AD lesions had strongly activated microglia, which expressed high levels of CD11b. They were associated with the plaque core. Immunostaining for complement proteins was weak in tg mice but very strong in AD deposits. We conclude that the weak inflammatory response and absence of NFTs indicate that tg mice are only a limited model of AD. Therapeutic strategies for the treatment of AD based on tg mouse models that overexpress Abeta may be limited in their application.     

Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis

With an Italian case series of 81 Italian patients and 130 controls, we analysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were maximal in females with early onset (EO) MG vs. controls [p<0.05, relative risk (RR)=9.9]. These patients showed neither a significantly high frequency of thymic hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies. The DRB1*03 allele was absent in patients with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients (p<0.005; RR=6.2), more frequent in females (p<0.005; RR=7.8) and most frequent in EOMG female patients (p<0.005; RR=15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype and its recombinants showed that the MHC region between C4 and TNF might contain genes that influence susceptibility to MG in females. Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subset of female MG patients. The combined effect of other intervening genes cannot be excluded.     

免疫机制与帕金森病关系的研究

目的　探讨免疫机制与帕金森病 (PD)发病的相关性。方法　采用PD患者的血清IgG建立PD的细胞模型 ,将纯化的PD患者、疾病对照组患者及正常人的血清IgG或 /及补体加入大鼠胚胎中脑神经元 胶质细胞混合培养体系中 ,通过MTT法检测细胞活力 ,免疫细胞化学法评价多巴胺 (DA)能细胞的数目、形态。结果　单独PDIgG(6 0 μg/ml)或补体对原代中脑神经元 胶质细胞混合培养体系中的DA能神经元的数目、形态无明显影响 (P >0 0 5 ) ;当培养体系同时接受二者处理时 ,抗酪氨酸羟化酶 (TH)阳性细胞数明显减少 (P <0 0 1) ,突起明显减少和缩短 ,β tubulin阳性细胞数和形态无明显变化 (P >0 0 5 ) ,总的细胞活力无明显下降(P >0 0 5 ) ,PDIgG(0、2 0、6 0、10 0 μg/ml)依赖补体对DA能神经元的毒性作用呈剂量依赖性。疾病对照组和正常对照组的血清IgG即使在补体存在时对TH阳性细胞数、形态也无明显影响 (P >0 0 5 )。结论　在补体存在时 ,用PDIgG可建立PD的细胞模型 ,提示PD的发病可能涉及免疫机制     

Increased in vitro uptake of the complement C3b in the serum of patients with Guillain-Barré syndrome, myasthenia gravis and dermatomyositis

To examine the role of complement in certain autoimmune neuromuscular diseases, we used an in-vitro quantitative complement uptake assay that allows measurement of the capacity of patients' sera to deposit fragments of the third complement component onto sensitized targets. C3 uptake was significantly higher in patients with active dermatomyositis, Guillain-Barré syndrome and myasthenia gravis, compared to inclusion body myositis and controls. The in-vitro C3 uptake assay supports the role of C3b neoantigen and Membranolytic Attack Complex deposition in the target tissues and may be a useful tool to monitor disease activity in patients with complement-mediated neurological disorders.     

Complement depletion suppresses Lewis rat experimental allergic neuritis

Lewis rats immunized with myelin and complete Freund's adjuvant were treated with cobra venom factor (CVF) which depletes the C3 component of complement. CVF given at day 9 delayed the onset of experimental allergic neuritis (EAN) by 2-3 days and when given at days 9 and 12 delayed the onset of EAN by 4-5 days. Lumbar nerve roots of CVF-treated rats had significantly less demyelination than those from control EAN rats.     

Complement Factor H Y402H polymorphism is associated with an increased risk of mortality after intracerebral hemorrhage

Intracerebral hemorrhage (ICH) accounts for 10% to 15% of all strokes and is a major cause of morbidity and mortality. Despite advances in management, numerous clinical trials have failed to demonstrate significant benefit of medical and surgical interventions, underscoring the need for the identification of novel therapeutic targets based on improved understanding of ICH pathophysiology and optimal risk stratification based on reliable and effective prognosticators. The alternative complement cascade has been implicated as an important contributor to neurological injury after ICH. Therefore, common, functionally relevant genetic variants in the key components of this pathway have been associated with greater inflammation post-ictus, further cerebral damage, and ultimately, a worse outcome. We investigated the affects of single-nucleotide polymorphisms (SNP) on mortality in complement component 3 C3 (rs2230199), complement component 5 C5 (rs17611), and Complement Factor H (CFH; rs1061170) genes, which are associated with the onset and progression of several neurological diseases, in a prospective cohort of patients with spontaneous ICH. From February 2009 through May 2010, adult patients with spontaneous ICH were admitted to the Columbia University Neurological Intensive Care Unit and enrolled in the Intracerebral Hemorrhage Outcomes Project. Demographic, clinical, radiographic, and treatment data were prospectively collected. Buccal swabs were obtained, and isolated cells were sequenced for the aforementioned SNP. A total of 103 patients were admitted with ICH, and of these, 82 consented for genetic testing and were included in the analysis. The median age was 61 years and 39% were females. The median Glasgow Coma Scale score on admission was 11.5. The CFH SNP was significantly associated with both discharge (p = 0.01) and 6-month mortality (p = 0.02), while no such association was observed for C3 (p = 0.545 and p = 0.830) or C5 (p = 0.983 and p = 0.536) SNP. Additionally, after controlling for pertinent variables identified in the univariate analysis, the CFH genotype independently predicted mortality at discharge (p = 0.019, odds ratio [OR] 7.62, 95% confidence interval [CI] 1.40–41.6) and at 6 months (p = 0.041, OR 1.822, 95% CI 1.025–3.239). The CFH genotype was also independently predictive of survival duration (p = 0.041, OR 1.822, 95% CI 1.025–3.239). We concluded that CFH Y402H polymorphism independently predicts mortality at discharge and 6-months and survival duration after spontaneous ICH.