SPINAL CORD REPAIR--MICROVASCULAR DYNAMICS & OXYGEN TRANSPORT POSTTRANSPLANTATION

脊髓修复——微血管动力学

• 批准号: 6112042
• 负责人: BRADFORD T STOKES
• 金额: --
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112042
• 关键词: autoradiography; blood flow measurement; cytochrome oxidase; deoxyglucose; disease /disorder model; gait; hemodynamics; laboratory rat; longitudinal animal study; microcirculation; nervous system regeneration; nervous system transplantation; nonhuman therapy evaluation; oxygen transport; psychomotor function; spinal cord injury; startle reaction

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.

细胞微环境在移植介导的修复中的作用 最近才被检查过。 我们以前使用过解剖学和 修复的生理指标，以探讨潜在的作用， 微血管发育和组织氧合在这个动态过程中。 我们以前的数据显示了低氧的阶段特异性外观， 移植后1周内胎儿移植物的微环境 随着这种胚胎微环境的扩展， 宿主组织 在另一组实验中，我们发现， 胚胎细胞移植到一个良好表征的脊髓模型， 脊髓损伤在同一时间段内引起行为改变（参见 初步数据和附录）。 在本提案中，我们希望建立 如果移植物的微血管成分和其他指标的发展 功能（血流量，细胞色素氧化酶组织化学和2- 脱氧葡萄糖放射自显影）可以与修饰 在恢复过程中的运动行为。 具体而言，解剖学和行为/功能的组合 分析将被用来检查悬浮移植的影响 早期（1天）挫伤损伤后的胎儿（14天）脊髓细胞， 亚慢性（10天）和慢性（28天）时间。 此后 技术组合将探讨：（1）纵向发展 条件性四足运动（增益分析）长达6个月 损伤后，（2）不自主运动反应（声学 惊吓），否则可能被脊柱损伤后遗症所掩盖，（3） 微血管成分的定量发育， 成功的移植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， 移植物大小（口服尼莫地平给药）同时改变这些 行为，和（5）如果生理指标（血流量，细胞色素 氧化酶组织化学，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 神经组织移植后 通过检查这些变化在移植物介导的修复中的作用，我们可以 继续定义功能条件， 移植会成功的 此外，我们可以直接测试 假设微血管动力学和氧运输 与成功的移植物发育和 自发的或条件性的行为模式。 的目标和 这一建议假设性结构与 项目1、4和5。