神经营养素—4在成年猴脑中的分布特征及其与成体中枢神经系统的功能关系

背景：神经营养素—4(NT—4，Neurotrophin -4)在神经系统的发育和成体中均起重要作用，不仅对某些特定亚群神经元的存活、增殖、分化及轴突可塑性有一定的调节作用，而且对某些神经元的生存也是必需的。但这些资料大多来源于体外实验，其在体内的作用尚不十分清楚，NT—4在体内的分布也少见报道，在高等灵长类猴脑的研究尚未见报道。目的：为探讨NT—4在成年灵长类动物猴脑的分布及为进一步研究NT—4与成体中枢神经系统的功能关系提供了有用的形态学依据。设计：用PBS代替一抗的实验对照。地点和材料：实验在昆明医学院神经科学研究所实验室完成。动物来自中科院昆明动物研究所的成年雄性恒河猴(体质量平均6kg)7只。方法：采用氯氨酮肌肉注射麻醉，Zamboin’s液心脏灌注固定，取脑组织各部位行冷冻切片，厚25μm。免疫组织化学SP法，抗体为兔抗NT—4多克隆抗体。主要观察指标：光镜下于猴脑的不同部位观察NT—4—IR阳性物(呈棕色串珠状、丝状或颗粒状)。对照实验用0．05mol／L PBS代替一抗行免疫组化染色。结果：NT—4—IR(Neurotrophin -4 immunoreactive)分布于大脑皮层Ⅲ～Ⅴ层的部分神经元胞体及突起以及自质内少量的神经胶质细胞；小脑皮质及自质内的部分神经元；海马CA1、CA2、CA3区的部分神经元；此外豆状核、尾状核、脑桥核、前庭神经核、薄束核、契束核、副神经核等可见散在阳性反应细胞及交织成网的纤维。结论：NT—4—IR广泛地分布于猴脑的多种组织和细胞，提示其功能可能涉及不同类型的神经元及可能的非神经元。     

脊髓损伤大鼠后肢功能恢复与内源性神经营养素表达之间的关系

目的：观察随着脊髓不完全损伤后大鼠后肢功能恢复，内源性神经营养因子表达的变化。 方法：实验于1998-04／09在解放军第三军医大学野战外科研究所完成。Wistar大白鼠44只，脊髓功能观测组12只；脊髓形态观察组32只，随机分为正常组2只、手术假伤组15只和脊髓腹侧损伤组15只。脊髓功能观测组12只和脊髓腹侧损伤组15只造脊髓损伤模型；手术假伤组15只进行造模处理，但不损伤脊髓。脊髓功能观测组于脊髓受压前及脊髓受压迫损伤后6，24，72h，7，14，21d对受试动物进行后肢行为功能评定。脊髓形态观察组32只实验动物进行免疫组织化学染色．随机计数50个细胞，观察神经营养素脑源性神经营养因子、胶质细胞源性神经营养因子、神经生长因子、神经营养素3的表达。 结果：44只实验大鼠均进入结果分析。①脊髓致伤后受试动物后肢出现明显瘫痪，随着时间的延长，脊髓功能得到逐步恢复。其中以伤后3-14d脊髓功能恢复最快，以后恢复较缓慢。②自伤后3h开始，脑源性神经营养因子、胶质细胞源性神经营养因子、神经生长因子、神经营养素3的表达开始增加，并于伤后72h达到高峰；1周内神经营养素维持在相对较高的表达水平，2周后这几种神经营养素的表达明显减弱[伤后3h：（14．82&;#177;4．93），（9．77&;#177;4．97），（2．27&;#177;1．85），（10．35&;#177;5．56）；伤后72h：（45．22&;#177;15．61），（34．54&;#177;12．56），（13．89&;#177;7．58），（33．2&;#177;11．53）；伤后1周：（31．94&;#177;12，82），（15．69&;#177;11．53）．（7．17&;#177;4．92），（16．74&;#177;13．2）；伤后2周：（14．02&;#177;7．36），（6．97&;#177;4．05），（2．27&;#177;1．87），（9．7&;#177;5．62）]。 结论：伤后脊髓组织内源性神经营养因子的过度表达参与了伤后2周内脊髓功能的快速恢复，但内源性神经营养因子的表达是短暂的．延续内源性神经营养因子的表达有望进一步促进脊髓功能恢复。     

脊髓损伤大鼠后肢功能恢复与内源性神经营养素表达之间的关系

目的:观察随着脊髓不完全损伤后大鼠后肢功能恢复,内源性神经营养因子表达的变化。方法:实验于1998-04/09在解放军第三军医大学野战外科研究所完成。Wistar大白鼠44只,脊髓功能观测组12只;脊髓形态观察组32只,随机分为正常组2只、手术假伤组15只和脊髓腹侧损伤组15只。脊髓功能观测组12只和脊髓腹侧损伤组15只造脊髓损伤模型;手术假伤组15只进行造模处理,但不损伤脊髓。脊髓功能观测组于脊髓受压前及脊髓受压迫损伤后6,24,72h,7,14,21d对受试动物进行后肢行为功能评定。脊髓形态观察组32只实验动物进行免疫组织化学染色,随机计数50个细胞,观察神经营养素脑源性神经营养因子、胶质细胞源性神经营养因子、神经生长因子、神经营养素3的表达。结果:44只实验大鼠均进入结果分析。①脊髓致伤后受试动物后肢出现明显瘫痪,随着时间的延长,脊髓功能得到逐步恢复。其中以伤后3～14d脊髓功能恢复最快,以后恢复较缓慢。②自伤后3h开始,脑源性神经营养因子、胶质细胞源性神经营养因子、神经生长因子、神经营养素3的表达开始增加,并于伤后72h达到高峰;1周内神经营养素维持在相对较高的表达水平,2周后这几种神经营养素的表达明显减弱[伤后3h:(14.82±4.93),(9.77±4.97),(2.27±1.85),(10.35±5.56);伤后72h:(45.22±15.61),(34.54±12.56),(13.89±7.58),(33.2±11.53);伤后1周:(31.94±12.82),(15.69±11.53),(7.17±4.92),(16.74±13.2);伤后2周:(14.02±7.36),(6.97±4.05),(2.27±1.87),(9.7±5.62)]。结论:伤后脊髓组织内源性神经营养因子的过度表达参与了伤后2周内脊髓功能的快速恢复,但内源性神经营养因子的表达是短暂的,延续内源性神经营养因子的表达有望进一步促进脊髓功能恢复。     

水中平板步行训练对脊髓损伤大鼠运动功能及脑源性神经营养因子、神经营养素-3表达的影响

目的探讨水中平板步行训练在脊髓损伤（SCI）大鼠康复中的作用及其与脊髓可塑性的关系。 方法将40只成年雄性Sprague-Dawley大鼠分为假模组、模型对照组、水疗训练组、减重平板训练组及水中平板训练组,每组8只。建立大鼠脊髓挫伤模型,各训练组于术后1周开始进行8周的康复训练。采用BBB评分、爬网格试验评定大鼠后肢功能的恢复,采用免疫组织化学方法检测大鼠脊髓中脑源性神经营养因子（BDNF）、神经营养素-3（NT-3）的表达。 结果水中平板训练组大鼠后肢运动功能较其他组明显改善（P<0.05）。3个训练组大鼠脊髓前角神经元BDNF及NT-3的表达与模型对照组相比均显著增加（P<0.05）。BDNF的表达在3个训练组之间两两比较,差异均无统计学意义（P&rt;0.05）。水中平板训练组NT-3的表达明显高于减重平板训练组（P<0.05）;而水中平板训练组与水疗训练组相比,差异无统计学意义（P&rt;0.05）。 结论水中平板训练可能通过影响BDNF及NT-3的表达增强脊髓损伤大鼠脊髓可塑性,促进后肢运动功能的恢复。     

胶质细胞系源性神经营养因子在神经元发育中的生物学功能

目的：考察胶质细胞系源性神经营养因子及其信号传导通路在神经元发育过程中的生物学功能，以及其中的分子机制。 资料来源：应用计算机检索Medline 1993-01／2005-10期间与胶质细胞系源性神经营养因子及其信号通路在神经元发育中的功能有关的文章，检索词“glia cell line-derived neurotrophic factor（GDNF）”分别和“neural survival，neural differentiation，neural migration，cell programmed death（apoptosis），RET，NCAM，mechanism”组合检索，并限定文章语言种类为English。 资料选择：就检索到的700余篇文献进行筛选，以胶质细胞系源性神经营养因子及其信号通路在神经元发育中的生物学功能为主要内容的文献350多篇。其中研究内容与神经元存活，分化，迁移密切相关，以近5年且发表在较权威杂志者优先。 资料提炼：最终选定105篇相关的文献，其中72篇检索到全文．而将其中观点相似的进行比较，以19篇近期发表的，叙述详尽的入选以进行综述。 资料综合：胶质细胞系源性神经营养因子受体有GFRα和RET两类亚基，通过胶质细胞系源性神经营养因子／GFRα1信号传导通路能够促进神经元的存活、分化及正确迁移，除RET外神经系统内还存在新型的跨膜受体及复杂的胞内信号转导通路。 结论：胶质细胞系源性神经营养因子对各种原因造成损伤后的神经细胞有保护和修复作用，在正常的神经元发育过程中也起到重要的作用。在神经系统发育中胶质细胞系源性神经营养因子存在多种相互关联的信号传导通路．能够促进发育中神经元的存活、分化及正确迁移。     

神经营养因子和免疫分子在中枢神经系统修复中的作用

神经营养因子在突触水平、轴突水平和细胞水平．乃至神经系统的附属结构水平上，可以调节中枢神经系统的再生。关于神经系统的免疫分子，新近的研究显示，中枢神经系统不是免疫豁免器官，中枢神经系统的免疫反应对中枢神经系统的再生有促进作用，一些原来被认为只有在免疫系统中存在的大分子还被证明参与中枢神经系统的发育与再生，而且不依赖于免疫系统。因此，作者推测神经营养因子和免疫分子间存在相互作用。     

神经前体细胞在成年小鼠脊髓颈段的分布特征

目的观察和分析在成年动物脊髓颈段的神经前体细胞（NPCs）分布特征。方法采用巢蛋白第二内含子增强子控制的LacZ启动子转基因小鼠和LacZ染色及阳性细胞量化技术，观察分析脊髓颈段的NPCs分布特征。结果NPCs在成年小鼠的整个脊髓颈段都可见，但是在不同区其数量和密度不同，在后角最多，其次是中央管，前角和侧角最少。在脊髓后角区NPCs主要分布在胶状质，在中央管NPCs主要分布在室管膜带，在脊髓髓质（白质）区很少，灰质明显比白质多，左右两边无明显差别。结论在NPCs的分布可能与临床疾病脊髓的损伤和修复有相关性，NPCs分布少的区易于损伤且难于修复，像前角和侧角。在后角、中央管和神经胶质细胞分布最多，则难于损伤，较易修复。     

胶质细胞系源性神经营养因子在神经元发育中的生物学功能

目的:考察胶质细胞系源性神经营养因子及其信号传导通路在神经元发育过程中的生物学功能,以及其中的分子机制。资料来源:应用计算机检索Medline1993-01/2005-10期间与胶质细胞系源性神经营养因子及其信号通路在神经元发育中的功能有关的文章,检索词“gliacellline-derivedneurotrophicfactor(GDNF)”分别和“neuralsurvival,neuraldifferentiation,neuralmigration,cellprogrammeddeath(apoptosis),RET,NCAM,mechanism”组合检索,并限定文章语言种类为English。资料选择:就检索到的700余篇文献进行筛选,以胶质细胞系源性神经营养因子及其信号通路在神经元发育中的生物学功能为主要内容的文献350多篇。其中研究内容与神经元存活,分化,迁移密切相关,以近5年且发表在较权威杂志者优先。资料提炼:最终选定105篇相关的文献,其中72篇检索到全文,而将其中观点相似的进行比较,以19篇近期发表的,叙述详尽的入选以进行综述。资料综合:胶质细胞系源性神经营养因子受体有GFRα和RET两类亚基,通过胶质细胞系源性神经营养因子/GFRα1信号传导通路能够促进神经元的存活、分化及正确迁移,除RET外神经系统内还存在新型的跨膜受体及复杂的胞内信号转导通路。结论:胶质细胞系源性神经营养因子对各种原因造成损伤后的神经细胞有保护和修复作用,在正常的神经元发育过程中也起到重要的作用。在神经系统发育中胶质细胞系源性神经营养因子存在多种相互关联的信号传导通路,能够促进发育中神经元的存活、分化及正确迁移。     

神经营养因子和生长因子在神经干细胞中的研究进展

神经营养因子(neurotrophic factors,NF)包括神经生长因子(nerve growth factor,NGF)、脑源性神经营养因子(brain-derived neural neurotrophic factor,BDNF)等。生长因子(growth factors,GF)家族成员有酸性成纤维细胞生长因子(acidic fibroblast growth factor,a FGF)、碱性成纤维细胞生长因子(basic fibroblast growth factor,b FGF)、血管内皮生长因子(vascular endothelial growth factor,VEGF)等,两大家族均对神经系统的发育以及维持神经干细胞(neural stem cells,NSCs)的存活、促进其增殖、分化并诱导其定向迁移等众多方面发挥着重要作用。本文简要概括介绍NF中的重要成员之一脑源性神经营养因子,GF家族中的重要成员VEGF和b FGF对NSCs的影响。     

Syngeneic central nervous system transplantation of genetically transduced mature, adult astrocytes

Advances in the development of highly infectious, replication-deficient recombinant retroviruses provide an efficient means of stable transfer of gene expression. Coupled with ex vivo transduction, surrogate cell populations can be readily implanted into the brain, thus serving as vehicles for delivering selected gene products into the central nervous system (CNS). Here we report that rat astrocytes can be routinely and safely isolated from brain tissue of a living donor by use of short-term gelatin sponge implants. The mature, nontransformed astrocytes were easily expanded, maintained in long-term tissue cultures and were efficiently transduced with an amphotropic retrovirus harboring a heterologous, fused transgene. In vitro retroviral infection rendered the nontransformed cells essentially 100% viable after exposure. The level of efficiency of infection (30-50% effective genome integration of provirus and expression of transgene in target cell populations) and minimal cell toxicity obviated the need to harvest large numbers of target cells. Cultured transduced astrocytes were resilient and exhibited select peptide expression for up to 1 year. Subsequently, transduced astrocytes were used in a series of experiments in which cells were transplanted intracerebrally in syngeneic animals. Post-implantation, astrocytes seeded locally and either insinuated into the surrounding parenchyma in situ or exhibited a variable degree of migration, depending on the anatomic source of astrocytes and the targeted brain implantation site. Transduced astrocytes remained viable in excess of 8 months post-transplantation and exhibited sustained transgenic peptide expression of green fluorescent protein/neomycin phosphotransferase in vivo. The sequential isolation and culture of nontransformed, mature, adult astrocytes and recombinant retrovirus-mediated transduction in vitro followed by brain reimplantation represents a safe and effective means for transferring genetic expression to the CNS. This study lays the foundation for exploring the utility of using a human autologous transplantation system as a potential gene delivery approach to treat neurological disorders. Prepared and utilized in this manner, autologous astrocytes may serve as a vehicle to deliver gene therapy to the CNS.     

骨髓基质细胞与中枢神经系统损伤和修复

目的:探讨骨髓基质细胞生物学特性、增殖分化能力和在中枢神经系统的多潜能应用及其作用机制。资料来源:应用计算机检索Medline1994-01/2004-12与骨髓基质细胞和中枢神经系统损伤和修复相关的文章,检索词“bonemarrowstemcells,centralnervoussystem,并限定文章语言种类为English,同时计算机检索万方数据库2000-01/2004-12相关的文章,限定文章语言种类为中文,检索词为“骨髓基质细胞,中枢神经系统”。资料选择:就检索到的200余篇文献进行筛选,选择以骨髓基质细胞用于中枢神经系统损伤和修复的基础研究为主要内容的文献60多篇,其中研究内容相似的,以近5年且发表在较权威杂志者优先,排除综述类文献和Meta分析。资料提炼:将筛选的22篇文献进行分类,7篇研究骨髓基质细胞的生物学特性,5篇与骨髓基质细胞增殖分化能力相关,10篇与骨髓基质细胞在中枢神经系统的应用及其作用机制相关。资料综合:骨髓基质细胞修复中枢神经系统损伤有巨大潜力。通过局部、脑室系统及动脉、静脉植入骨髓基质细胞均发现其在中枢神经系统内长时间存活并集中于损伤区,且有着向神经细胞分化的表现。脑内特殊微环境对其迁移、分化起着重要的诱导作用,同时通过移植骨髓基质细胞可改善损伤的神经功能,此外,骨髓基质细胞对中枢神经系统的神经干细胞也有积极的影响作用,可促进神经再生及可塑性的增强。但目前在骨髓基质细胞的分离、鉴别等方面还存在一些问题有待解决。结论:骨髓基质细胞具有多向分化潜能,在适宜条件下可分化为神经元和星形胶质细胞,能在人类中枢神经系统疾病中起到修正和更改的潜在作用,但其对神经功能损伤恢复的具体机制仍不是十分明确。     

Neuropeptide Y: localization in the central nervous system and neuroendocrine functions

Neuropeptide Y (NPY) is a 36-amino acid peptide first isolated and characterized from porcine brain extracts. A number of immunocytochemical investigations have been conducted to determine the localization of NPY-containing neurons in various animal species including both vertebrates and invertebrates. These studies have established the widespread distribution of NPY in the brain and in sympathetic neurons. In the rat brain, a high density of immunoreactive cell bodies and fibers is observed in the cortex, caudate putamen and hippocampus. In the diencephalon, NPY-containing perikarya are mainly located in the arcuate nucleus of the hypothalamus; numerous fibers innervate the paraventricular and suprachiasmatic nuclei of the hypothalamus, as well as the paraventricular nucleus of the thalamus and the periaqueductal gray. At the electron microscope level, using the pre- and post-embedding immunoperoxidase techniques, NPY-like immunoreactivity has been observed in neuronal cell body dendrites and axonal processes. In nerve terminals of the hypothalamus, the product of the immunoreaction is associated with large dense core vesicles. In lower vertebrates, including amphibians and fish, neurons originating from the diencephalic (or telencephalic) region innervate the intermediate lobe of the pituitary where a dense network of immunoreactive fibers has been detected. At the ultrastructural level, positive endings have been observed in direct contact with pituitary melanotrophs of frog and dogfish. These anatomical data suggest that NPY can act both as a neurotransmitter (or neuromodulator) and as a hypophysiotropic neurohormone. In the rat a few NPY-containing fibers are found in the internal zone of the median eminence and high concentrations of NPY-like immunoreactivity are detected in the hypothalamo-hypophyseal portal blood, suggesting that NPY may affect anterior pituitary hormone secretion. Intrajugular injection of NPY causes a marked inhibition of LH release but does not significantly affect other pituitary hormones. Passive immunoneutralization of endogenous NPY by specific NPY antibodies induces stimulation of LH release in female rats, suggesting that NPY could affect LH secretion at the pituitary level. However, NPY has no effect on LH release from cultured pituitary cells or hemipituitaries. In addition, autoradiographic studies show that sites for 125I-labeled Bolton-Hunter NPY or 125I-labeled PYY (2 specific ligands of NPY receptors) are not present in the adenohypophysis, while moderate concentrations of these binding sites are found in the neural lobe of the pituitary. It thus appears that the inhibitory effect of NPY on LH secretion must be mediated at the hypothalamic level.(ABSTRACT TRUNCATED AT 400 WORDS)     

Role of the central nervous system in the adult respiratory distress syndrome

The CNS might play an important pathophysiologic role in the induction of the adult respiratory distress syndrome (ARDS). Post-traumatic development of cerebral microthromboses seems to be a major feature. To test this hypothesis, we subjected Wistar rats with postburn ARDS to the following microneurosurgical procedures in an attempt to morphologically detect modifications in the evolving pattern: a) anterior (AH) or posterior (PH) hypothalamus nuclei stereotaxic electrolytic lesion; b) intracerebroventricular microinjections of phenoxybenzamine (PB)-50, micrograms propranolol-0.5 micrograms, cocaine-5 micrograms, epinephrine-0.5 micrograms, carbachol(CA)-5 micrograms, pirilamine-20 micrograms, cimetidine-30 micrograms, lidocaine-20 micrograms, atropine (AT)-40 micrograms; c) intra-AH microinjections of CA-10 micrograms, AT-20 micrograms; and d) intra-PH microinjections of PB-10 micrograms, norepinephrine-0.05 microgram. The results showed that the alpha-adrenergic components of PH induce a potentiation in ARDS whereas the cholinergic components of AH seem to attenuate this syndrome. This work suggests that a damaged CNS may suffer cybernetic derangements as to induce it to generate inappropriate adaptative responses that can result in the development of ARDS.     

原发性中枢神经系统淋巴瘤的MRI

目的：探讨免疫功能正常人原发性中枢神经系统淋巴瘤（PCNSL）的常规MRI表现。资料与方法：对21例经手术病理证实的PCNSL的MRI表现进行回顾分析，其中男14例，女7例，平均年龄49.6岁。结果：21例患者共检出30个病灶，其MRI表现具有如下特点：①病灶T1WI多呈低或等信号，T2WI呈等或稍高信号，单发或多发，境界清晰。②轻中度瘤周水肿，并可见“火焰样”特征性水肿。③增强后病灶多明显均匀强化；“缺口征”、“尖角征”的出现具有特异性。结论：传统MRI在PCNSL的诊断中起着重要的作用。     

Adult neural stem cells and repair of the adult central nervous system

Neural stem cells are present not only in the developing nervous systems, but also in the adult central nervous system of mammals, including humans. The mature central nervous system has been traditionally regarded as an unfavorable environment for the regeneration of damaged axons of mature neurons and the generation of new neurons. In the adult central nervous system, however, newly generated neurons from adult neural stem cells in specific regions exhibit a striking ability to migrate, send out long axonal and dendritic projections, integrate into pre-existing neuronal circuits, and contribute to normal brain functions. Adult stem cells with potential neural capacity recently have been isolated from various neural and nonneural sources. Rapid advances in the stem cell biology have raised exciting possibilities of replacing damaged or lost neurons by activation of endogenous neural stem cells and/or transplantation of in vitro-expanded stem cells and/or their neuronal progeny. Before the full potential of adult stem cells can be realized for regenerative medicine, we need to identify the sources of stem cells, to understand mechanisms regulating their proliferation, fate specification, and, most importantly in the case of neuronal lineages, to characterize their functional properties. Equally important, we need to understand the neural development processes in the normal and diseased adult central nervous system environment, which is quite different from the embryonic central nervous system, where neural development has been traditionally investigated. Here we will review some recent progress of adult neural stem cell research that is applicable to developmental neurobiology and also has potential implications in clinical neuroscience.     

Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system

Metabotropic glutamate (mGlu) receptors, which include mGlu1-8 receptors, are a heterogeneous family of G-protein-coupled receptors which function to modulate brain excitability via presynaptic, postsynaptic and glial mechanisms. Certain members of this receptor family have been shown to function as presynaptic regulatory mechanisms to control release of neurotransmitters. In general, Gi-coupled mGlu receptor subtypes appear to negatively modulate excitatory (and possibly also inhibitory) neurotransmitter output when activated. Localization studies have shown that mGlu7 is restricted to the presynaptic grid at the site of vesicle fusion. These studies along with other evidence suggest that mGlu7 is the nerve terminal autoreceptor that regulates physiological release of glutamate. Other mGlu subtypes, in particular mGlu2, mGlu8, and possibly mGlu4, are also localized presynaptically, but at perisynaptic sites outside the active zone of neurotransmitter release. Gi-coupled mGlu receptors also may exist on presynaptic elements of neighboring gamma-aminobutyric acid (GABA) neurons where they play a role in heterosynaptic suppressions of GABA release. This suggests that these receptors may have evolved to monitor glutamate that has "spilled" out of the synapse. Thus, they may serve as the brain's evolutionary mechanism to prevent pathological changes in neuronal excitability and thus maintain homeostasis. Recent progress on the molecular and pharmacological aspects of these presynaptic mGlu receptors is unveiling their functions and the therapeutic directions of agents designed for these novel glutamate receptor targets.     

"肾生髓"与中枢神经系统功能的关系

目的 从神经生理学角度,探讨中医"肾生髓"的本质 ,为"肾生髓"理论提供科学依据. 方法 2.5月龄 SD雄性大鼠,以单纯随机方法分成正常对照组、去势组和虚劳组.用听觉脑干诱发电位( ABR)、体感诱发电位( SEP)以及氨基酸类和单胺类中枢递质含量为指标,观察虚劳肾虚和去势肾虚模型大鼠的中枢神经系统( CNS)功能状况. 结果肾虚模型大鼠睾酮( T)水平下降时,虚劳组 [(271± 20) mg]胸腺质量明显低于正常对照组 [(565± 81) mg](P< 0.01).与对照组比较,肾虚模型大鼠神经系统功能下降,表现为造模后 ABR峰潜伏期延长( F=6.713,P< 0.001) , 阈值提高( F=9.555, P< 0.001); SEP的峰潜伏期延长( F=4.161, P=0.002),差异有非常显著性意义.中枢递质含量下降. 结论肾虚时血 T水平低下影响 CNS的兴奋性,这一作用可能是"肾"(性腺激素)通过调制某些中枢递质的合成与释放而产生效应的结果.     

Growth factor enhanced retroviral gene transfer to the adult central nervous system

The use of viral vectors for gene delivery into mammalian cells provides a new approach in the treatment of many human diseases. The first viral vector approved for human clinical trials was murine leukemia virus (MLV), which remains the most commonly used vector in clinical trials to date. However, the application of MLV vectors is limited since MLV requires cells to be actively dividing in order for transduction and therefore gene delivery to occur. This limitation precludes the use of MLV for delivering genes to the adult CNS, where very little cell division is occurring. However, we speculated that this inherent limitation of ML V may be overcome by utilizing the known mitogenic effect of growth factors on cells of the CNS. Specifically, an in vivo application of growth factor to the adult brain, if able to induce cell division, could enhance MLV-based gene transfer to the adult brain. We now show that an exogenous application of basic fibroblast growth factor induces cell division in vivo. Under these conditions, where cells of the adult brain are stimulated to divide, MLV-based gene transfer is significantly enhanced. This novel approach precludes any vector modifications and provides a simple and effective way of delivering genes to cells of the adult brain utilizing MLV-based retroviral vectors.