SPINAL CORD REPAIR--MICROVASCULAR DYNAMICS & OXYGEN TRANSPORT POSTTRANSPLANTATION

细胞微环境在移植介导的修复中的作用 最近才被检查过。我们以前用过解剖学和 探讨生理指标对修复的潜在作用 这一动态过程中的微血管发育和组织氧合作用。 我们之前的数据显示了一个特定阶段的低氧现象 早在移植后1周胎儿移植物的微环境 随着这种胚胎微环境的延伸到周围 宿主组织。在另一组实验中，我们发现 将胎儿细胞移植到具有良好特性的脊髓模型中 在同一时间段内，脊髓损伤会引起行为改变(参见 初步数据和附录)。在这项提案中，我们希望建立 如果移植物的微血管元素和其他指标的发育 功能(血流、细胞色素氧化酶组织化学和2- 脱氧葡萄糖放射自显影)可以与 恢复过程中的运动行为。 具体地说，解剖学和行为学/功能的结合 分析将用于检查悬浮移植的效果。 胎儿(14天)脊髓细胞挫伤后早期(1天)， 亚慢性(10天)和慢性(28天)。此后，A 结合技术将探索：(1)纵向发展 长达6个月的条件四足运动(增益分析) 损伤后，(2)不自主运动反应(声学)的改变 惊吓)，否则可能会被脊柱损伤的后遗症掩盖，(3) 微血管元素的数量发展似乎是 成功的移植物整合和行为表达的一个因素，(4) 增加微血管发育程度的因素是如何 移植物的大小(口服尼莫地平)伴随着改变这些 行为，以及(5)生理指标(血流、细胞色素 2-脱氧葡萄糖放射自显影) 分化与解剖学和行为学变化有关 在神经组织移植之后。 通过研究这种变化在移植物介导的修复中的作用，我们可以 继续定义在以下情况下的功能条件 移植将会蓬勃发展。此外，我们还可以直接测试 微血管动力学和氧运输是 与成功的移植物发育和改变 自发的或条件性的行为范式。目标和目标 这一提议的假设结构与 项目1、4和5。

The role of the cellular microenvironment in transplant-mediated repair has only recently been examined. We have previously used anatomical and physiological indices of repair to explore the potential role of microvascular development and tissue oxygenation in this dynamic process. Our previous data have shown a stage specific appearance of a low oxygen microenvironment in fetal grafts as early as 1 week post-transplantation with an extension of this embryonic microenvironment into surrounding host tissue. In another set of experiments, we have found that transplantation of fetal cells into a well-characterized model of spinal cord injury evokes behavioral modifications in this same time period (see preliminary data and appendix). In this proposal, we wish to establish if the development of microvascular elements and other indices of graft function (blood flow, cytochrome oxidase histochemistry and 2- deoxyglucose autoradiography) can be associated with the modification of motor behaviors during the recovery process. Specifically, a combination of anatomical and behavioral/functional analyses will be used to examine the effects of suspension transplants of fetal (14 day) spinal cells after contusion lesions at early (1 day), sub-chronic (10 day), and chronic (28 days) times. Thereafter a combination of techniques will explore: (1) the longitudinal development of conditioned quadrupedal locomotion (gain analysis) for up to 6 months post-injury, (2) the alterations in involuntary motor responses (acoustic startle) that may otherwise be masked by sequelae to spinal injury, (3) the quantitative development of microvascular elements that seem to be one factor in successful graft integration and behavioral expression, (4) how factors that increase the extent of microvascular development and graft size (oral nimodipine administration) concomitantly modify these behaviors, and (5) if physiological indices (blood flow, cytochrome oxidase histochemistry, 2-deoxyglucose autoradiography) of graft differentiation are associated with the anatomical and behavioral changes following neural tissue transplantation. By examining the role of such changes in graft-mediated repair, we can continue the definition of the functional conditions under which transplants will prosper. Furthermore, we can directly test the hypothesis that microvascular dynamics and oxygen transport are associated with successful graft development and the alteration of spontaneous or conditioned behavioral paradigms. The aims and hypothetical construct of this proposal are directly related to those of Projects 1, 4, and 5.