神经系统轴突三维定向生长的数值模拟

目的研究轴突在三维组织中的定向生长问题,探讨轴突沿非平坦基底定向生长时基底的低起伏程度对轴突的生长速率、成束和解束速率的影响。方法根据实验观察,设轴突生长的牵引力与靶细胞分泌的可扩散吸引分子的浓度梯度成正比,轴突成束和解束的侧向力与生长锥分泌的可扩散吸引分子和排斥分子的浓度梯度成正比,并且,吸引力指向浓度高的方向,排斥力指向浓度低的方向,浓度满足扩散方程。对于非平坦基底,有效力为沿基底轮廓线的切向分量。数值计算采用三维有限差分法和改进的Euler法。结果(1)轴突在三维组织中定向生长的基本特征与在二维培养基实验中的观察是一致的,只是在形态上有三维与二维之分;(2)非平坦基底的低起伏程度影响轴突的生长,随着起伏加剧,生长锥的前进速率减小、侧向速率增加。结论(1)许多基于二维培养实验所揭示的轴突生长的基本规律在三维情况下仍然是成立的;(2)基底的几何性质是影响轴突生长速率的重要因素之一。     

关于轴突生长的导向分子机理的探讨

在神经系统的发育过程中,轴突的生长具有严格的方向性。轴突沿特定的路线生长、延长,并伸向与它建立突触联系的靶细胞或神经元的胞体、树突或轴突。轴突末端称为生长锥,其扇形膨大部分称作板足,在板足的表面伸出许多细小的突起,称为丝足。板足的细胞骨架主要是由微管构成,丝足的细胞骨架主要是不成束的肌动蛋白(图1)。生长锥对周围环境极其敏感,其表面受体可识别细胞外基质中或周围细胞上的导向分子。这些导向分子中,有的能够吸引生长锥向其生长,有的却是排斥生长锥向其生长,生长锥就在这样一个复杂的环境中,选择一条正确的路径到达目的地。     

放射治疗下实体肿瘤演变的数学模型和数值模拟

目的数值模拟研究放射治疗下放射敏感性系数、治疗频率、肿瘤细胞成熟年龄等因素对实体肿瘤放射治疗效果的影响。方法建立放射治疗下实体肿瘤演变的连续-离散混合数学模型,模型考虑肿瘤的微环境(氧、细胞外基质、基质降解酶)以及自身行为(增殖、凋亡、黏附)对肿瘤演变的影响,并引入线性二次模型描述肿瘤对放射治疗的响应,采用数值模拟方法模拟不同条件下肿瘤演变的过程,评价放射治疗的疗效。结果肿瘤的放射治疗效果与放射敏感性系数、肿瘤细胞成熟年龄正相关,而在放射剂量总量不变的情况下,高频治疗和低频治疗效果并没有特别明显的区别。结论模拟结果与临床结果相吻合,可为肿瘤放射治疗的理论及临床研究提供一种新的方法。     

轴突生长诱向因子(Netrin)基因家族研究进展

<正> 在神经系统发育过程中,神经与其靶细胞之间精确联系的形成是依靠多种细胞外诱向因子介导实现的。这些因子通过作用于轴突生长锥上的相应受体而诱导或排斥轴突生长,从而决定了轴突的生长路线以及轴突与特定靶细胞的功能联系。Netrin基因家族是此类因子的代表之一,根据位于轴突生长锥上的Netrin受体不同,Netrin在神经发育的不同时     

可溶性PCP-2EC/Fc蛋白在神经粘附和轴突生长中的促进作用

为了探讨酪氨酸磷酸酶PCP- 2在神经粘附和轴突生长中的作用,本实验构建了PCP- 2胞外区与人免疫球蛋白IgGFc融合蛋白表达载体,在哺乳动物细胞中表达并纯化PCP- 2EC/Fc蛋白,进行荧光球聚集实验,然后以PCP 2胞外区融合蛋白作为基质,观察其对原代培养神经元的粘附和轴突生长的影响。结果显示,PCP- 2胞外区可同源粘附,对原代培养神经元的粘附和轴突生长有促进作用,提示PCP -2作为同源介导的神经粘附分子,可能在维持正常神经的功能和促进损伤神经的修复中发挥重要作用。     

神经系统动力学数学模型的研究进展

随着人们对大脑研究的进一步深入,诞生了神经系统动力学这一门新兴学科,大脑的数学模型是该学科研究的基础。本文介绍了一系列具有代表性和广阔应用范围的神经元数学模型,并就此展开讨论,对其发展前景作了展望;最后,将其与复杂网络研究相结合,提出了有价值的研究方向。     

雪旺氏细胞对中枢神经轴突生长的支持和促进作用

胚胎大鼠脊髓植块接种于纯度〉９５％的单层人胎儿雪旺氏细胞表面进行培养，观察雪旺氏细胞对神经突起生长的支持作用，脊髓神经突起在雪旺氏细胞表面活跃生长，突起生长速度〉４５０μｍ／天，与对照组相比有显著性差异。将长于鼠尾胶上的雪旺氏细胞移植于成年大鼠脊髓损伤腔内，移植后２１天后，透射电镜观察，有髓或无髓纤维长人移植物中，移植后３０天，长入移植物中的轴突更丰富，而无细胞的胶原移植物中未见轴突长入。结果表明     

呼吸道内颗粒物沉积的数值模拟

目的通过数值模拟方法研究人呼吸过程中吸入的颗粒物在呼吸道内的沉积规律及其影响因素。方法建立正常人呼吸道三维数值模型,模拟吸气过程中气流在呼吸道内的分布规律。在鼻孔或口等气流入口处释放颗粒,模拟悬浮颗粒物随着吸入气流在呼吸道内的沉积过程。同时改变颗粒物直径、密度、呼吸气流速率等参数,通过对比分析,研究颗粒物在呼吸道内沉积的影响因素。结果颗粒物在呼吸道内主要沉积在鼻阈、固有鼻腔气道中部、鼻咽部以及支气管内壁,并且颗粒物的沉积率随着其直径、密度、呼吸气流速率的增大而增加,几个参数对沉积率的影响程度也不相同。结论颗粒物在呼吸道内主要沉积在气道几何形状复杂或者气道走向剧烈改变的位置,颗粒物的直径、密度、呼吸气流速率均会影响到其在呼吸道内的沉积率。研究结果可为空气污染引发呼吸道疾病风险的临床评估提供数值依据。     

冠状动脉中氧输运的数值模拟研究

利用正常人的CT数据,通过图像分割和重建建立右侧冠状动脉的真实三维几何模型;利用专业的网格划分软件ICEM CFD 12.0对几何模型进行计算网格的划分;利用商用CFD软件Fluent12.0对模型中的血液流动和氧输运进行数值模拟,获得了在入口的平均速度为0.2m/s的定常流情况下,冠状动脉内的流线图、壁面切应力分布图、重要截面上的速度分布和氧浓度分布图。数值模拟结果发现,在血管曲率较大的区域和血管分叉区域的血液流动较为复杂,存在二次流、回流和死水区;在弯曲血管附近靠近内侧的区域的氧浓度显著降低、浓度梯度也降低。这些结果与临床上观察到的这些区域易形成冠状动脉粥样硬化斑块的结论相吻合。     

冠状动脉移植管的血流动力学数值模拟

采用有限元数值计算的方法，模拟了冠状动脉搭桥术中移植管内的生理流动。计算模型包括了冠状动脉狭窄，并考虑了由于移植管直径大于冠状动脉直径而在两者缝合时移植管的变形。计算结果分析了缝合区附近的流场、二次流、壁面切应力在心动周期内的时空分布情况。计算结果表明，在缝合前端下游，存在一个低切应力、高切应力梯度的区域，在缝合区底部存在一个高切应力、高切应力梯度的区域。这两个区域都是内皮细胞增生并造成移植管术后再阻塞的危险部位。     

Numerical simulation of a compartmental system for the distribution of lipid soluble chemicals in mammalian tissues.

An analysis of the stability and accuracy of a particular numerical scheme used in the mathermatical modeling of the flow limit pharmacodynamics of highly lipid soluble drugs in mammalian tissue systems is presented. The necessary definitions and theorems together with their proofs are included. A typical example of the flow limit pharmacodynamics of the highly lipid soluble drug dieldrin (HEOD) is also presented.     

Initial stages of retinofugal axon development in the hamster: evidence for two distinct modes of growth

Summary In order to characterize differences in growth patterns of axons as they elongate toward their targets and during the initial stages of terminal arbor formation within the targets, we examined the primary visual system of fetal and newborn hamsters using three morphological methods: the Cajal-deCastro reduced silver method, the rapid Golgi technique, and anterograde transport of HRP. Axons emerge from the retina between the 10th and 11th embryonic days (E10–E11). The front of retinal axons crosses the chiasm, extends over the primitive dorsal nucleus of the lateral geniculate body (LGBd) by E13, and advances to the back of the superior colliculus (SC) by E13.5–E14. The rate of axon growth during this advance is nearly 2 mm/day. Collateral sprouts appear on axons around E15.5. In the LGBd and SC, these sprouts arise from multiple sites along the parent axons. Only one or a few of the sprouts continue to grow and branch, while others are eliminated. The net rate of axon collateral advance in this second phase is an order of magnitude slower than during the stage of axon elongation. Thus, formation of CNS projections may involve two qualitatively distinct modes of axon growth. The arborization mode contrasts with the elongation mode by the presence of branching, a lack of fasciculation and a slower average rate of extension. The Stereotypic direct advance of axons during elongation also differs from the remodelling which occurs during arborization. The delay between axon arrival at targets and onset of arborization could be a reflection of axons waiting for a maturational change to occur in the retina or in targets. Arborization in the LGBd and SC is initiated around the same time, implicating the former possibility. However, a slower differentiation of retinal arbors in the SC, in addition to morphological differences of arbors in the two structures, suggests that alterations in substrate factors also play a critical role in triggering the early stages of arbor formation.     

Effect of cervical spinal cord hemisection on the expression of axon growth markers

To evaluate the plasticity processes occurring in the spared and injured tissue after partial spinal cord injury, we have compared the level of axon growth markers after a C2 cervical hemisection in rats between the contralateral (spared) and ipsilateral (injured) cervical cord using western blotting and immunohistochemical techniques. In the ipsilateral spinal cord 7 days after injury, although GAP-43 levels were increased in the ventral horn caudal to the injury, they were globally decreased in the whole structure (C1–C6). By contrast, in the contralateral intact side 7 days and 1 month after injury, we have found an increase of GAP-43 and βIII tubulin levels, suggesting that processes of axonal sprouting may occur in the spinal region contralateral to the injury. This increase of GAP-43 in the contralateral spinal cord after cervical hemisection may account, at least partially, to the spontaneous ipsilateral recovery observed after a cervical hemisection.     

Selective central nervous system tropism of primary central nervous system lymphoma

Primary Central nervous system lymphoma (PCNSL) is most frequently a diffuse large B cell lymphoma (DLBCL), which is confined to the Central nervous system (CNS). We performed an experiment in which lymphoma cells from a PCNSL patient were implanted subcutaneously in an athymic mouse. The lymphoma cells were shown to home to the CNS with histologic evaluations of the brain showing multiple large B cells in blood vessels consistent with intravascular large B cell lymphoma (IVL). We did not find any evidence of lymphoma at the site of implantation or other locations. The findings are consistent with highly selective tropism of PCNSLforthe CNS and its vasculature.     

Stretch growth of integrated axon tracts: Extremes and exploitations

Although virtually ignored in the literature until recently, the process of ‘stretch growth of integrated axon tracts’ is perhaps the most remarkable axon growth mechanism of all. This process can extend axons at seemingly impossible rates without the aid of chemical cues or even growth cones. As animals grow, the organization and extremely rapid expansion of the nervous system appears to be directed purely by mechanical forces on axon tracts. This review provides the first glimpse of the astonishing features of axon tracts undergoing stretch growth and how this natural process can be exploited to facilitate repair of the damaged nervous system.     

数值模拟松质骨中流动电势分布

目的对压力驱动下一种松质骨细观模型产生的流动电势进行数值模拟分析,了解流动电势在松质骨中的分布特点。方法根据电场和流体的控制方程,利用有限单元法计算该松质骨模型在一定压力下产生的稳态流动电势。结果松质骨模型中靠近固体表面的流动电势较大,约为43.4μV;而远离固体表面的流动电势较小,约为19.7μV。压力和Zeta电势对模型的流动电势影响比较大,并且呈线性增长的关系。离子数浓度较低时,离子数浓度对流动电势的影响较大;当离子数浓度较高时,离子数浓度对流动电势的影响很小。结论研究结果为利用电流、电磁场刺激等方法防治和治疗临床骨折、老年性骨质疏松及其他骨科疾病提供相关的理论依据。     

糖链结构在神经系统中的功能作用

糖链作为生物信息分子参与细胞生物几乎所有的生命和疾病过程，起特异性的识别、介导、调控等信号转导作用。神经系统发育、神经网络形成、神经再生连接和神经肌肉连接等方面都涉及糖链的参与。糖链在神经系统中发挥着不可取代的作用，而且糖链又因其结构的多样性、复杂性和微观不均一性引起其功能在神经系统中的多样性。     

Parasitic diseases of the central nervous system

Parasitic infections, though endemic to certain regions, have over time appeared in places far removed from their original sites of occurrence facilitated probably by the increase in world travel and the increasing migration of people from their native lands to other, often distant, countries. The frequency of occurrence of some of these diseases has also changed based on a variety of factors, including the presence of intermediate hosts, geographic locations, and climate. One factor that has significantly altered the epidemiology of parasitic diseases within the central nervous system (CNS) is the HIV pandemic. In this review of the pathology of parasitic infections that affect the CNS, each parasite is discussed in the sequence of epidemiology, life cycle, pathogenesis, and pathology.