胰岛素样生长因子-1与癫痫相关性的研究进展

癫痫是神经系统常见疾病之一,癫痫发作可导致脑损伤已被动物实验和临床观察证实。 胰岛素样生长因子-1（IGF-1）是神经营养保护因子,在中枢神经系统的生长、发育、分化、损伤后修复中 起到重要作用,然而它在癫痫发作中所起的作用存在争议,现回顾目前IGF-1 与癫痫相关研究,对IGF-1 与癫痫关系进行系统综述。     

胰岛素样生长因子-1与缺血性脑血管病

胰岛素样生长因子 - 1(IGF - 1)是一种重要的促神经生长因子 ,具有多种生物学功能。脑缺血发生后 ,IGF - 1在脑组织的含量与分布发生明显变化 ,并可能通过一系列有效机制参与保护缺血性脑损伤 ,展现了一定的临床应用前景     

胰岛素样生长因子-1与创伤性脑损伤

胰岛素样生长因子-1(IGF-1)是一种脑保护因子,它对神经系统的生长、发育及损伤后的保护具有重要的意义。正常脑组织中IGF-1系统的表达十分广泛,脑损伤后IGF-1在脑内的含量及分布均发生明显变化,显示其参与了脑损伤的病理生理过程,体内、外实验也充分证实IGF-1具有明显的神经保护作用。探讨IGF-1给药的途径和剂量,将为创伤性脑损伤(TBI)的治疗开辟一条新途径。     

胰岛素样生长因子对脊髓损伤的保护作用

胰岛素样生长因子 (Insulin likegrowthfactors ,IGFs)由 2个多肽类生长因子IGF Ⅰ、IGF Ⅱ构成。大量实验证实 ,IGFs能维护神经细胞的生存 ,促进神经纤维的生长、分化、修复、再生。本文就有关脊髓损伤后内源性IGFs的变化及意义 ,外源性IGFs对脊髓损伤的作用进行综述。     

胰岛素样生长因子-1与阿尔茨海默病关系研究进展

胰岛素样生长因子-1(IGF-1)在神经营养方面的作用为人所熟悉。近年的研究发现,IGF-1与阿尔茨海默病(AD)以及认知功能关系密切。本研究就IGF-1在体内的分布、与AD的关系,以及影响AD可能的机制等方面,对其发挥的主要作用进行综述。     

胰岛素样生长因子-Ⅰ系统和肌萎缩侧索硬化

目的:胰岛素样生长因子-Ⅰ(IGF-Ⅰ)是一种作用于多个组织和器官的多向性蛋白质,具有促进有丝分裂、刺激蛋白质和蛋白多糖的合成、DNA和RNA的合成以及促进细胞增殖和分化的作用。IGF-Ⅰ调节细胞代谢受胰岛素样生长因子结合蛋白(IGFBPs)的调控,通过IGF受体发挥生理作用。肌萎缩侧索硬化(ALS)是一种致死性神经系统疾病,以脊髓、脑干、运动皮层运动神经元逐渐变性丢失为特征。ALS病因不清,目前有许多假说,其中被大多数认可的学说是运动神经元缺乏必需的营养因子,导致神经元变性、丢失以及靶肌肉萎缩。ALS患者的外周和中枢的IGF-Ⅰ系统均有较大改变。IGF-Ⅰ治疗ALS的离体实验和在体实验效果显著,目前多中心正在进行IGF-Ⅰ治疗ALS患者的三期临床试验。     

胰岛素样生长因子-1在神经系统变性病中的作用

<正>胰岛素样生长因子-1(Insulin-ike growth factor 1,IGF-1)是一个7. 5 kD a的肽类激素,它主要在肝脏产生,受垂体分泌的生长激素调节。IGF-1在神经的形成和发育过程中起到重要作用。大部分脑内IGF-1被认为是在低密度脂蛋白受体相关蛋白1 (LRP1)和低密度脂蛋白受体相关蛋白2(LRP2)分子的帮助下从血浆中通过血脑屏障转运而来的~([1])。海马的IGF-1水平与血清中IGF-1水平明显相关,提     

精神分裂症患者血清胰岛素样生长因子水平分析

目的探讨精神分裂症患者血清胰岛素样生长因子(insulin-like growth factors,IGFs)水平与精神病理症状的关系。方法研究共纳入精神分裂症患者41例(患者组)和健康受试者40例(对照组),采用阳性与阴性症状量表(PANSS)评估患者精神病性症状,使用酶联免疫吸附法(ELISA)测定血清IGF-1和IGF-2水平。结果患者组血清IGF-1和IGF-2含量均显著低于正常对照组(P<0.05)。相关性分析发现,患者血清IGF-1水平与PANSS阳性症状评分负性相关(r=-0.462,P=0.026),而血清IGF-2水平则与阴性症状评分负性关联(r=-0.395,P=0.034)。结论精神分裂症患者血清IGFs水平存在异常,并与精神病理症状有关,提示IGFs参与精神分裂症的病理过程,可能是疾病症状评估的生物学指标。     

胰岛素样生长因子-1在中枢神经系统疾病中的保护作用

胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)在神经系统的生长、分化、修复和再生中起重要作用.近年来,研究表明IGF-1对神经系统具有保护作用其在中枢神经系统疾病中具有重要意义.     

遗传性运动感觉神经病合并心肌肥大的研究

遗传性运动感觉神经病合并心肌肥大的研究崔毅郑惠民金军谢惠君丁素菊刘莹我们对遗传性运动感觉神经病（ＨＭＳＮ）合并肥厚性心肌病（ＨＣＭ）一家系三代１２例患者及１例无症状者进行肌电图（ＥＭＧ），神经传导速度（ＮＣＶ），大脑局部血流量（γＣＢＦ），脑干听觉诱...     

Immunohistochemical study of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) in choroid plexus papilloma

Abstract

Insulin-like growth factor-ll (IGF-II), a mitogen for various kinds of cells, has been shown to be secreted from the choroid plexus in animals. Insulin-like growth factor binding protein-2 (IGFBP-2), one of the six carrier proteins for IGFs, is also thought to be released from the choroid plexus, bind to IGF-II in the cerebrospinal fluid (CSF) and modulate the action of this growth factor. Little is known about the expression and localization of these substances in human choroid plexus and choroid plexus papillomas. The present immunohistochemical study demonstrated all six choroid plexus papillomas were positive for IGF-II, whereas normal choroid plexuses were negative for IGF-II. On the other hand, IGFBP-2 was positive in the endothelium and vascular media in the normal choroid plexus, while it was weakly positive in four and negative in two out of six choroid plexus papillomas. These results suggest that the alterations in the IGF-II/ IGFBP-2 axis might be involved in the tumorigenesis of choroid plexus papilloma. [Neurol Res 1999; 21: 339-344]     

不同途径应用胰岛素样生长因子1对新生大鼠缺氧缺血性脑损伤的影响

目的 研究不同途径应用胰岛素样生长因子1（IGF-1）对新生大鼠缺氧缺血性脑损伤（HIBD）的影响。方法 40只新生大鼠分为4组：HIBD模型对照组（对照组）、静脉注射组、经鼻腔滴入组和假手术组：给药组于缺氧后分别给予尾静脉注射和经鼻腔滴入IGF-1 2．5μg（溶于生理盐水0．1ml中）;对照组于HIBD后给予等量的生理盐水尾静脉注射;假手术组仅分离颈总动脉,不结扎不缺氧。24h后处死取脑组织,免疫组化法观察脑组织caspase-3的表达,组织学方法观察脑组织病理改变情况。结果 与对照组相比,给药各组caspase-3表达减少（均P〈0．01）,神经细胞总数增加（均P〈0．01）,变性／坏死神经细胞数减少（均P〈0．01）,结论 静脉注射和鼻腔滴入IGF-1均可能通过降低HIBD脑组织中caspase-3表达,从而对HIBD脑组织损伤产生保护作用。     

Reduced brain insulin-like growth factor I function during aging

Peripheral insulin-like growth factor I (IGF-I) function progressively deteriorates with age. However, whereas deterioration of IGF-I function in the aged brain seems probable, it has not been directly addressed yet. Because serum IGF-I can enter into the brain through the cerebrospinal fluid (CSF), we examined this route of entrance in aged mice. To distinguish endogenous murine IGF-I from exogenously applied IGF-I, we used human IGF-I. We found that after intraperitoneous injection, CSF levels of human IGF-I were significantly higher in old mice (2 year-old) as compared to young ones (4-month-old). In spite of this increase capacity to take IGF-I from the circulation, brain and plasma IGF-I levels were reduced in naive old mice. Moreover, IGF-I signaling was deteriorated in the brain of aged animals. Basal as well as IGF-I-induced activation of the brain IGF-I receptor/Akt/GSK3 pathway was markedly reduced even though old mice have higher levels of brain IGF-I receptors. These data suggest that increases in brain IGF-I receptors and in the capacity to take up serum IGF-I result ineffective because IGF-I function is reduced and aged mice are cognitively impaired, a trait dependant on preserved serum IGF-I input to the brain.     

Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.     

Effects of insulin, insulin-like growth factor-II and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells

The identification of biologically important and chemically well-defined substances that can promote axon and dendrite formation would improve present understanding of the development of the nervous system. Physiological concentrations of insulin and insulin-like growth factor-II (IGF-II) reversibly enhanced neurite outgrowth (NTO) in human neuroblastoma SH-SY5Y cells cultured in media with and without serum. Nerve growth factor (NGF), in contrast, did not enhance NTO in serum-free media. Furthermore, anti-NGF antiserum inhibited NGF but not insulin-enhanced NTO. Insulin increased [3H]leucine and [3H]uridine uptake. These increases, together with increased NTO, were inhibited by cycloheximide and actinomycin D, respectively. The inhibition of NTO by cycloheximide was reversible. Human neuroblastoma cell lines that were responsive by NTO to NGF were also responsive to insulin, with the exception of line CHP-270. Moreover, cell lines unresponsive by NTO to NGF, and to tumor promoters, were uniformly unresponsive to insulin. These findings suggest that there are common defects in distal sites, because specific NGF and tumor promotor receptors are present in these lines. Insulin increased [3H]thymidine uptake in SH-SY5Y and CHP-100 cells. However, the enhancement of NTO by insulin and IGF-II in SH-SY5Y cells was independent of the cellular proliferation rate. Our results, together with the observations of others, suggest that insulin and IGF-II may modulate NTO in the nervous system.     

The insulin-like growth factor I system in the rat cerebellum: Developmental regulation and role in neuronal survival and differentiation

The developmental regulation of insulin-like growth factor I (IGF-I), its receptor, and its binding proteins (IGFBPs) was studied in the rat cerebellum. All the components of the IGF-I system were detectable in the cerebellum at least by embryonic day 19. Levels of IGF-I receptor and its mRNA were highest at perinatal ages and steadily decrease thereafter, although a partial recovery in IGF-I receptor mRNA was found in adults. Levels of IGF-I and its mRNA also peaked at early ages, although immunoreactive IGF-I showed a second peak during adulthood. Finally, levels of IGFBPs were also highest at early postnatal ages and abruptly decreased thereafter to reach lower adult levels. Since highest levels of the different components of the IGF-I system were found at periods of active cellular growth and differentiation we also examined possible trophic effects of IGF-I on developing cerebellar cells in vitro. We found a dose-dependent effect of IGF-I on neuron survival together with a specific increase of the two main neurotransmitters used by cerebellar neurons, GABA and glutamate. Analysis of cerebellar cultures by combined in vitro autoradiography and immunocytochemistry with cell-specific markers indicated that both Purkinje cells (calbindin-positive) and other neurons (neurofilament-positive) contain IGF-I binding sites. These results extend previous observations on a developmental regulation of the IGF-I system in the cerebellum and reinforce the notion of a physiologically relevant trophic role of IGF-I in cerebellar development. © 1994 Wiley-Liss, Inc.     

Differential adaptations of insulin-like growth factor-I, basic fibroblast growth factor, and leukemia inhibitory factor in the plantaris muscle of rats by mechanical overloading: an immunohistochemical study

We investigated changes in several growth factors in the rat plantaris muscle produced by mechanical overloading by ablation of synergists using immunohistochemistry. At 1 and 3 days post surgery, the insulin-like growth factor-I (IGF-I) level was slightly increased in the cytosol and markedly increased in the invading cells of the extracellular space. Thereafter, the IGF-I immunoreactivity evoked by overloading rapidly decreased to the normal level. The level of leukemia inhibitory factor (LIF), which was not shown to change at 1 day post surgery, was increased in the cytosol at 3, 5, 7 and 10 days and at 2 weeks. Basic fibroblast growth factor (bFGF) immunoreactivity did not change during the entire period of overloading (1 day–3 weeks post surgery). These results indicate that the elevations of the levels of IGF-I and LIF show differential time course in the plantaris muscle subjected to functional overload. Furthermore, bFGF appears not to be related to the compensatory hypertrophy produced by overloading. Received: 20 June 1997 / Revised, accepted: 8 September 1997     

Growth hormone-releasing peptide 6 protection of hypothalamic neurons from glutamate excitotoxicity is caspase independent and not mediated by insulin-like growth factor I

Treatment of the fetal hypothalamic neuronal cell line RCA-6 with growth hormone-releasing peptide 6, an agonist of the ghrelin receptor, or insulin-like growth factor I activates intracellular signalling cascades associated with anti-apoptotic actions. Abnormally high concentrations of glutamate provoke over-excitation of neurons leading to cell damage and apoptosis. Thus, the aim of this study was to investigate whether the administration of growth hormone-releasing peptide 6 and insulin-like growth factor I attenuates monosodium glutamate-induced apoptosis in RCA-6 neurons and the mechanisms involved. Two different mechanisms are involved in glutamate-induced cell death, one by means of caspase activation and the second through activation of a caspase-independent pathway of apoptosis mediated by the translocation of apoptosis-inducing factor. Growth hormone-releasing peptide 6 partially reversed glutamate-induced cell death but not the activation of caspases, suggesting blockage of the caspase-independent cell death pathway, which included interference with the translocation of apoptosis-inducing factor to the nucleus associated with the induction of Bcl-2. In contrast, the addition of insulin-like growth factor I to RCA-6 neurons abolished glutamate-induced caspase activation and cell death. These data demonstrate for the first time a neuroprotective role for growth hormone secretagogues in the caspase-independent cell death pathway and indicate that these peptides have neuroprotective effects independent of its induction of insulin-like growth factor I.