Recovery of sacral spinal reflexes after transplantation

描述(由申请人提供)：这是一个继续项目的修订申请，该项目旨在研究大鼠挫伤后阴茎和外肛门括约肌脊髓反射的功能恢复，旨在建立人类脊髓损伤(SCI)的模型。将骶骨反射的恢复与活动能力的恢复进行比较。5-羟色胺(5-羟色胺)能下行系统被认为参与了脊髓损伤后5-羟色胺(5-羟色胺)下行系统的恢复，在以前的资金支持阶段，有证据表明5-羟色胺(5-HT)对脊髓损伤后5-羟色胺(5-羟色胺)能神经元的去神经和再神经支配作用。5-羟色胺发芽的来源被认为是严重挫伤后残留在备用纤维边缘的少量轴突。 我们已经证明，胶质限制前体细胞(GRP)可以移植到挫伤中，并通过减少胶质瘢痕来改变损伤环境。修订后的意见书侧重于这样的假设，即脊髓损伤后将GRPs移植到挫伤损伤腔内将导致更多的5-羟色胺萌发，并将促进骶骨反射和运动的恢复。在目标1中，我们将比较接受挫伤损伤的大鼠在伤后9-10天接受与不接受GRP移植的大鼠的骶骨和运动功能的长期恢复情况。在目标2中，我们将比较接受和不接受GRP移植的大鼠已识别的肛门外括约肌(EAS)和球脊髓灰质炎(BS)运动神经元(MNS)的5-羟色胺能输入量。在目标3中，我们将用顺行示踪剂结合5-羟色胺免疫组织化学标记5-羟色胺的脑干来源，以检查发芽进入骶髓的来源。这也将使我们能够检验这样一种假设，即备用下行系统对脊髓的重新神经支配保持了原始连接的特异性。这些研究代表了研究脊髓损伤和发育生物学的实验室之间的合作，旨在为神经胶质前体移植在脊髓损伤中可能的治疗价值提供指导。

DESCRIPTION (provided by applicant): This is a revised submission of a request for continuation of a project aimed at studying functional recovery of penile and external anal sphincter ('sacral') spinal cord reflexes after contusion injuries in rats meant to model human spinal cord injury (SCI). Recovery of sacral reflexes was compared to recovery of locomotion. Serotonergic (5-HT) descending systems are thought to be involved in this recovery, and in the previous funding period, evidence was provided for denervation and reinnervation of sacral MNs by 5-HT after SCI. The source of the 5-HT sprouting is thought to be the small number of axons that remain in the spared rim of fibers after severe contusion SCI. We have shown that glial restricted precursor cells (GRPs) can be transplanted into contusion injuries, and that they alter the lesion environment by reducing glial scarring. The revised submission focuses on the hypothesis that the transplantation of GRPs into the contusion lesion cavity after SCI will result in more 5-HT sprouting and will enhance the recovery of sacral reflexes and locomotion. In aim 1, we will compare the long-term recovery of sacral and locomotor functions in rats receiving contusion lesions with and without GRP transplants given at 9-10 days following injury. In aim 2 we will compare the amount of serotonergic input to identified external anal sphincter (EAS) and bulbospongiosis (BS) motoneurons (MNs) in rats with and without GRP transplants. In aim 3, we will examine the source of the sprouting into the sacral cord by labeling brainstem sources of 5-HT with anterograde tracers combined with 5-HT IHC. This will also allow us to test the hypothesis that the reinnervation of the cord by spared descending systems maintains the specificity of the original connections. These studies represent a collaboration between laboratories studying SCI and developmental biology, and are intended to provide guidance on the possible therapeutic value of glial precursor transplantation in SCI.