炎性反应与癫痫

近年来研究显示炎性反应与癫痫的发生发展密切相关。炎性反应使血脑屏障完整性被破坏,通透性增加,白细胞浸润;胶质细胞活化、增生,分泌大量的促炎性细胞因子并上调其相关受体,这些反应进一步使神经元兴奋性增高,诱导癫痫发作。炎性反应产生的细胞兴奋性毒性,诱发神经元死亡,破坏脑组织,形成海马硬化等病理改变。炎性反应还使病程迁延反复,产生对常规抗癫痫药物的抵抗等。本文主要对炎性反应与癫痫发生、发展的关系及相关治疗做一综述。     

炎性反应与癫痫

越来越多的研究显示炎性反应与癫痫的发病密切相关。在炎性反应过程中,血脑屏障完整性被破坏,通透性增加,白细胞浸润;胶质细胞活化、增生,分泌大量的促炎性细胞因子并上调其相关受体。这些反应进一步使神经元兴奋性增高,诱导癫痫发作;产生细胞兴奋性毒性,诱发神经元死亡,破坏脑组织,形成海马硬化等病理改变;使病程迁延反复,产生对常规抗癫痫药物的抵抗等。本文主要对炎性反应与癫痫发生、发展的关系及相关治疗做一综述。     

循环Micro RNA在缺血性卒中炎性反应通路中调控作用的研究进展

缺血性卒中(ischcmic stroke,IS)是一种由脑血管狭窄或完全阻塞而导致的脑组织缺血性坏死及神经功能损伤的疾病,其重要的病理生理机制之一为炎性反应。炎性反应通过调控下游信号通路促进IS的发生、发展。Micro RNA是一类18～24个核苷酸大小的非编码RNA,参与调节基因的转录与翻译。越来越多的研究证实,Micro RNA在IS炎性反应通路的调控中发挥关键作用。现就Micro RNA在IS炎性反应通路调控作用的相关研究做一综述,为防治IS提供新策略。     

炎性反应和凝血因子在急性脑血管病中的作用及应用价值

<正> 炎性反应及凝血因子与急性脑血管病(acute cerebralvascular disease,aCVD)的发生、发展密切相关。超敏C反应蛋白(high sensitive-C reactive protein,hs-CRP)、纤维蛋白原(fibrinogen,Fib)与CVD的相关性研究较少,且结论并不一致。该研究通过测定aCVD患者hs-CRP和Fib水平,初步探讨炎性反应以及凝血因子在aCVD中的作用。     

C型凝集素受体参与出血性卒中炎性脑损伤的作用机制及前景展望

巨噬细胞诱导的C型凝集素（macrophage-inducible C-type lectin，Mincle）受体是模式识别受 体家族的重要成员，可以识别从坏死细胞中释放的自配体，并与下游的脾酪氨酸激酶（Spleen tyrosine kinase，Syk）作用激活单独信号通路，引发一系列炎性反应。越来越多的实验数据表明，Mincle/Syk信 号转导通路参与了包含卒中在内的多种神经系统疾病的炎症反应，特异性的抑制该通路激活可以抑 制神经炎症，修复神经功能损伤。本文主要对Mincle作用机制和病理研究进展进行综述，并对Mincle 对出血性卒中的治疗作用进行展望。     

Toll样受体4在乙醇所致的小胶质细胞激活中的作用

滥用乙醇可以导致脑损害以及神经系统退行性变,但是其对脑损害的神经性炎性反应方面机制的研究还不明确。近年相关研究结果显示小胶质细胞作为中枢神经系统的主要炎性细胞,在乙醇所致的神经性炎性反应中作用非常重要。Toll样受体4(TLR4)是固有免疫系统中的一个重要模式识别受体,在脑损害和神经系统退行性变中起到重要作用。乙醇通过TLR4信号通路激活小胶质细胞,诱导炎性反应介质释放和细胞死亡而导致脑损害,抑制TLR4信号通路可能对减轻乙醇所致的神经性炎性损害具有重要意义。本文对Toll样受体4在乙醇所致的小胶质细胞激活中的作用做一综述。     

动脉粥样硬化与炎性因子

动脉粥样硬化(AS)是一种全身性、弥漫性的血管壁疾病,主要是动脉管壁内胆固醇酯大量堆积形成粥样硬化斑块,导致血管壁增厚和狭窄。AS容易诱发心、脑血管疾病。越来越多的研究提示AS是一个血管受损后的炎性反应过程,有关血浆炎性标志物的研究在国内外已广泛展开,众多炎性因子已成为心脑血管病的预测因子。本文就与AS相关的炎性标志物的分类及作用机制作一综述。     

颅咽管瘤组织炎性反应与临床病理和肿瘤预后相关性分析

目的 探讨颅咽管瘤不同炎性反应等级与临床病理、肿瘤预后的相关性.方法 根据临近肿瘤正常组织交界处的炎性反应细胞数量对颅咽管瘤进行炎性反应评估,结合临床资料,对49例经手术治疗的颅咽管瘤病例进行回顾性分析并探讨其与临床病理和肿瘤预后的相关性.结果 颅咽管瘤组织炎性反应与肿瘤病理类型(x2=6.603,P =0.037)、全切率(x2=8.188,P=0.017)、钙化(γ=0.326,P=0.022)、术后患者下丘脑功能评分(γ=0.376,P=0.008)和手术难易度(γ =0.515,P＜0.001)相关.结论 颅咽管瘤起源、生长方式及组织炎性反应程度可能是决定颅咽管瘤预后的重要因素.     

炎性反应在缺血性脑损伤中的作用和机制

尽管已有大量关于脑缺血的研究见诸文献,但仍缺乏有效的治疗方法,对其发病机制的理解亦不充分。许多研究提示,炎性反应在缺血性脑损伤中起关键作用,因此炎性反位业已成为治疗缺血性卒中最具潜力的靶点之一。近年来,一系列研究揭示了关于炎性反应在缺血性脑损伤中作用的重要新概念:(1)虽然大部分炎性反应可以加剧缺血性脑损伤,但亦有一些炎性反应对缺血脑组织有益。     

散发性包涵体肌炎研究进展

最近的研究提示散发性包涵体肌炎的发病机制可能与免疫炎性反应、细胞变性、异常蛋白聚集、线粒体异常等有关,对于包涵体肌炎的诊断主要依赖病理诊断,免疫调节治疗可能有效。本文就包涵体肌炎发病机制的研究、临床表现及治疗等有关方面的最新进展进行了简要综述。     

Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120

Chronic brain inflammation is the common final pathway in the majority of neurodegenerative diseases and central to this phenomenon is the immunological activation of brain mononuclear phagocyte cells, called microglia. This inflammatory mechanism is a central component of HIV-associated dementia (HAD). In the healthy state, there are endogenous signals from neurons and astrocytes, which limit excessive central nervous system (CNS) inflammation. However, the signals controlling this process have not been fully elucidated. Studies on the peripheral nervous system suggest that a cholinergic anti-inflammatory pathway regulates systemic inflammatory response by way of acetylcholine acting at the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) found on blood-borne macrophages. Recent data from our laboratory indicates that cultured microglial cells also express this same receptor and that microglial anti-inflammatory properties are mediated through it and the p44/42 mitogen-activated protein kinase (MAPK) system. Here we report for the first time the creation of an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. Furthermore, this activation, as measured by TNF-alpha and nitric oxide (NO) release, is synergistically attenuated through the alpha7 nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. Our findings suggest a novel therapeutic combination to treat or prevent the onset of HAD through this modulation of the microglia inflammatory mechanism.     

Sepsis associated encephalopathy

The sepsis associated encephalopathy (SAE) is a common cause of delirium, accompanied by hyperthermia or not. It is defined as a diffuse cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct infectious involvement of the central nervous system. It is, thus, a diagnosis of exclusion. The pathogenic mechanisms underlying SAE are now better understood: it involves, at least, an intense inflammation of the central nervous system and a major impairment of the blood brain barrier. At the present time, clinical, biological and radiological characteristics of SAE have been sufficiently described to ensure rapid identification, but prognosis remains severe. Proper management requires treatment as early as possible of the infectious site and accompanying systemic inflammatory response. When appropriately conducted, minimal consequences or complete recovery can be expected.     

Role of gap junctions in chronic pain

Gap junctions are specialized transmembrane channels that allow rapid electrical signalling and direct intercellular communication for maintenance and coordination of normal cellular activities and homeostasis. Although gap junction channels in the nervous system mediate intercellular coupling between glial cells and between neurons, they also contribute to the spread of secondary damage and inflammation under pathological conditions. There is now evidence of the involvement of gap junctions in chronic pain caused by nervous system damage or tissue inflammation. In this Mini-Review, we highlight recent studies demonstrating the dynamic plasticity of gap junctions in response to nervous system injury and the effects of gap junction blockade on neuronal survival and modulation of pain in animal models of neuropathic and inflammatory pain. The involvement of dorsal root ganglia and spinal cord gap junctions in mediating chronic pain and the potential for targeting connexins as a novel modality for the treatment of intractable pain syndromes arising from nervous system injury and disorders are discussed.     

Immunolocalization of vgr (BMP-6, DVR-6), a TGF-β related cytokine,to Schwann cells of the rat peripheral nervous system: Expression patterns are not modulated by autoimmune disease

The transforming growth factors type β (TGF-β) have been implicated in regulation of peripheral nervous system inflammation and regeneration. Here we demonstrate expression of a TGF-β-related bone morphogenetic protein, the vgr (BMP-6, DVR-6) in Schwann cells of the rat peripheral nervous system. The expression of vgr in the peripheral nervous system suggests that this factor and probably other TGF-β-related bone morphogenetic proteins might participate in Schwann cell function during aspects of peripheral nervous system physiology and pathology. However, we did not observe changes in expression patterns in response to autoimmune inflammation (experimental autoimmune neuritis) of the peripheral nervous system. © 1995 Wiley-Liss, Inc.     

Vasculitis of the nervous system

Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PNS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PMS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. “Primary angiitis of the CNS” is the term used to describe isolated CNS involvement by vasculitis, in which neither the clinical presentation and behaviour of the disease, nor the histopathology is uniform. This heterogeneity indicates a spectrum, depending on the type and extent of the vascular involvement seen within the CNS, covering a group of disorders, rather than a single disease. This may explain the different prognosis and response to treatments.. In clinical practice vasculitis of the nervous system, secondary to a known cause or underlying disease is more commonly seen than as a primary disorder. Primary systemic vasculitides and connective-tissue disorders, Behçet's Disease, lymphoproliferative diseases and other malignancies, some infections and related conditions, drugs and substance abuse are some of the conditions known to cause vasculitis in the nervous system. There is a broad variety of pathogenetic mechanisms. Both the CNS and the PNS may be involved, either separately or together.     

Inflammation and gliosis in neurological diseases--clinical implications

The inflammatory reaction accompany all acute processes in the central nervous system (CNS), (as stroke or traumatic brain injury) and chronic neurodegenerative processes (as Parkinson's or Alzheimer's disease), and through the stage of cleaning of damage tissue, contribute to recovery and regeneration and eventually to restoration of the function. However many studies showed that inflammation in the CNS may be harmful because of an excessive vulnerability of the nervous tissue or impaired regulation. Manipulation of the inflammation is now one of the approaches in the treatment of the various diseases of the CNS.     

Intracerebroventricular Transplantation of Embryonic Neuronal Tissue from Inflammatory Resistant into Inflammatory Susceptible Rats Suppresses Specific Components of Inflammation

To more directly define the role of central nervous system factors in susceptibility to peripheral inflammatory disease, we examined the effect of intracerebroventricular transplantation of neuronal tissue from inflammatory resistant into inflammatory susceptible rats on subcutaneous carrageenan-induced inflammation (a measure of innate immunity), and on the relative percentage of naive and memory T helper cells in peripheral blood (a measure of the anamnestic immune response). Female inflammatory disease susceptible Lewis (LEW/N) rats transplanted with hypothalamic tissue from inflammatory resistant Fischer (F344/N) rats exhibited >85% decrease in carrageenan inflammation compared to naive LEW/N rats, LEW/N rats transplanted with F344/N spinal cord, or sham-operated animals. LEW/N rats transplanted with LEW/N hypothalamic tissue exhibited >50% decrease in carrageenan inflammation. In contrast, intracerebroventricular transplantation of neuronal tissue did not affect the characteristically twofold higher percentage of naive versus memory T helper cells in LEW/N rats, suggesting that the central nervous system (CNS) and hypothalamus play a greater role in the innate inflammatory response than in the acquired immune processes. Grafted tissue survived well and did not show extensive gliosis or inflammation. Compared to naive LEW/N rats, LEW/N rats transplanted with F344/N or LEW/N hypothalamic tissue expressed significantly greater hypothalamic corticotropin releasing hormone mRNA. LEW/N rats transplanted with F344/N hypothalamic tissue also showed significant increases in plasma corticosterone responses to lipopolysaccharide. These data indicate that intracerebroventricular transplantation of fetal hypothalamic tissue from inflammatory resistant into inflammatory susceptible rats suppresses peripheral inflammation partially through hypothalamic factors. These findings have implications for understanding the contribution of specific neuronal tissue in regulation of components of the immune/inflammatory response and in susceptibility to inflammatory disease. Furthermore, this model could be used in the development of potential new treatments for inflammatory/autoimmune diseases aimed specifically at sites within the CNS.     

Inflammatory mechanism in ischemic neuronal injury

Inflammation has been implicated as a secondary mechanism underlying neuronal injury induced by ischemia. A variety of experimental models, including thromboembolic stroke, focal and global ischemia, have been used to evaluate contributions of inflammation to neuronal damage. The vasculature endothelium promotes inflammation through upregulation of adhesion molecules such as intercellular adhesion molecule （ICAM）, E-selectin, and P-selectin that bind to circulating leukocytes and facilitate migration of leukocytes into the central nervous system （CNS）. Once being in the CNS, leukocytes produce cytotoxic molecules that promote cell death. The response of macrophages and microglia to injury may either be beneficial by scavenging necrotic debris or be detrimental by facilitating cell death of neurons that would otherwise recover. While many studies have tested these hypotheses, the significance of inflammation in stroke models is inconclusive. This review summarizes data regarding roles of cell adhesion molecules, astrocytes, microglia and leukocytes in stroke.     

Brain-immune interactions and ischemic stroke: clinical implications

Increasing evidence shows that the central nervous system and the immune system interact in complex ways, and better insight into these interactions may be relevant to the treatment of patients with stroke and other forms of central nervous system injury. Atherosclerosis, autoimmune disease, and physiological stressors, such as infection or surgery, cause inflammation that contributes to vascular injury and increases the risk of stroke. In addition, the immune system actively participates in the acute pathogenesis of stroke. Thrombosis and hypoxia trigger an intravascular inflammatory cascade, which is further augmented by the innate immune response to cellular damage occurring in the parenchyma. This immune activation may cause secondary tissue injury, but it is unclear whether modulating the acute immune response to stroke can produce clinical benefits. Attempts to dampen immune activation after stroke may have adverse effects because central nervous system injury causes significant immunodepression that places patients at higher risk of infections, such as pneumonia. The activation of innate immunity after stroke sets the stage for an adaptive immune response directed against brain antigens. The pathogenic significance of adaptive immunity and its long-term effects on the postischemic brain remains unclear, but it cannot be ruled out that a persistent autoimmune response to brain antigens has deleterious and long-lasting consequences. Further research will be required to determine what role, if any, immunity has in long-term outcomes after stroke, but elucidation of potential mechanisms may open promising avenues for the development of new therapeutics to improve neurological recovery after brain injury.     

Inflammatory mechanism in ischemic neuronal injury

1 Molecular mechanisms participating in ischemic neuronal damage Ischemic stroke results from a transient or permanent reduction in cerebral blood flow (CBF) that is restricted to the territory of a major brain artery. The reduction in blood flow is, in most cases, caused by the occlusion of a cerebral artery either by an embolus or by local thrombosis. A num- ber of biomolecular events, including glutamate release, increases in intracellular calcium and massive production of free radicals, a…