RECOVERY OF FUNCTION AFTER SPINAL CORD DAMAGE

拟议研究的目的是确定 有助于脊髓损伤后功能的恢复。通过开发 方法来增强这些机制，我们将尝试增加 恢复的程度。我们将检查轴突切断术的两个后果 对恢复很重要：1)轴突切断后的细胞存活和2)对 支持轴突生长的存活细胞。我们将研究的因素 影响细胞存活的因素有：a)靶点的影响；b) 传入的影响；c)未受损神经元的萌发；d)变化 在蛋白质合成方面。数量形态和电生理 将使用各种方法来识别存活细胞的特征 并对再生所需的反应进行表征。这个 将测试天然靶点和传入物质对细胞存活的影响 使用体内和体外方法，然后我们将确定 提供胎儿组织的替代靶点将增加发生 神经元存活和轴突生长。植物的萌发和突触发生 损伤所幸免的未受损神经元也可以调节恢复。 通过补偿；萌芽的一些功能后果将是 测试过。 为了研究提高恢复速度的方法，我们将确定 与再生相关的轴突切断细胞的变化 回应。我们将使用电生理方法，原位杂交 并研究了蛋白质合成的变化，以表征成功 再生反应，我们还将检查刺激因素 发育中的神经元中的轴突生长。我们将使用胎儿脊髓 移植以确定移植的组织如何鼓励 支持轴突细胞再生的代谢活动。这个 脊髓再生所介导的功能后果 移植的胎儿组织的存在将通过定量评估 开发了评估运动行为恢复的方法。除了……之外 在这六个项目中，我们提出了六个核心设施，包括新的 以组织培养、图像分析和运动分析为核心。这些核心 设施将为所有项目提供先进技术，以及 促进分析回收率的新方法的发展 脊髓损伤后的功能。建议的实验计划应该是 允许确定一些潜在的恢复和恢复机制 制定加强这些机制的方法，以增加 脊髓损伤后的恢复程度。

The purpose of the proposed research is to determine the mechanisms which contribute to recovery of function after spinal cord injury. By developing methods which can enhance these mechanisms, we will attempt to increase the extent of recovery. We will examine two consequences of axotomy that are important to recovery: 1) cell survival after axotomy and 2) responses of the surviving cells that support axonal growth. Factors that we will study that affect cell survival are: a) the influence of the target; b) the influence of afferents; c) sprouting of undamaged neurons; and d) changes in protein synthesis. Quantitative morphological and electrophysiological methods will be used to identify characteristics of cells that survive axotomy and to characterize the responses required for regeneration. The influence of natural targets and afferents on cell survival will be tested using in vivo and in vitro methods; we will then determine whether supplying a surrogate target of fetal tissue will enhance the likelihood of neuronal survival and axonal outgrowth. Sprouting and synaptogenesis of undamaged neurons which are spared by the lesion can also mediate recovery by compensation; some of the functional consequences of sprouting will be tested. In order to investigate methods for enhancing recovery we will identify changes in axotomized cells that are correlated with the regenerative response. We will use electrophysiological methods, in situ hybridization and studies of protein synthetic changes to characterize the successful regenerative response, and we will also examine the factors that stimulate axonal outgrowth in developing neurons. We will use fetal spinal cord transplants to identify the way in which the transplanted tissue encourages metabolic activity supportive of regeneration by axotomized cells. The functional consequences of spinal cord regeneration mediated by the presence of transplanted fetal tissue will be assessed using quantitative methods developed to evaluate recovery of motor behavior. In addition to the six projects, we are proposing six core facilities, including new tissue culture, image analysis and motion analysis cores. These core facilities will make advanced technology available to all projects, and promote development of new methods for the analysis of the recovery of function after spinal cord injury. The proposed experimental program should permit identification of some of the mechanisms underlying recovery and development of ways to enhance these mechanisms in order to increase the extent of recovery following spinal cord injury.