Restoration of Postural Control After Spinal Cord Injury

项目摘要/摘要 无法保持直立的身体姿势和平衡是以下主要运动障碍之一 脊髓损伤(SCI)。在我们之前的NIH支持的研究中，脊柱手术中的特定扭曲 与脊髓休克相关的三种主要现象中每一种的姿势机制(网络)， 在动物模型中已经证实了痉挛的发展和姿势功能的恢复 (兔子)。我们还展示了脊柱上体位网络在体位控制中的重要作用。一位将军 本项目的目的是在脊髓损伤引起的基础上解释脊髓损伤对姿势功能的影响。 相应的棘上神经元姿势网络的运作变化。临床数据显示 大多数SCI都是不完整的。不完全的SCI会导致大脑之间的相互作用严重扭曲 和脊髓。这会导致肌肉张力和肢体姿势反射的显著降低或不对称。 导致无法站立和保持平衡。我们的目标1是分析不完全SCI的影响 (外侧和背侧半切，LHS和DHS)关于脊柱上姿势网络的操作，以及 通过特定上行和下行路径的活动变化来解释姿势缺陷。我们 已经开发出一种新的技术，允许重复多次执行“可逆的LHS或DHS”。这 允许研究姿势反应和上行和下行的单个神经元的活动 在两种情况下的通路：(I)当大脑连接到脊髓时和(Ii)在LHS或DHS期间， 当脊髓和大脑之间通过侧径或背径的连接分别是 暂时被屏蔽了。以前我们已经证明，在DHS和LHS之后，姿势功能在几个月内恢复 几周。我们的目标2是分析恢复的LHS-和DHS-的棘上姿势网络的活动。 受试者，并通过特定种群上升和恢复活动的变化来解释恢复 下降的神经元。为此，我们将(I)记录脊髓上的单个神经元的活动 恢复的LHS和DHS受试者在姿势表现时的姿势网络，以及(Ii)比较 结果与正常受试者和急性期LHS和DHS受试者的结果一致。我们的目标3是分析 不同下行通路在控制恢复期LHS患者特定姿势行为中的作用 和DHS受试者，并通过特定通路的功能作用变化来解释恢复。为 为此，不同脊髓上通路的化学发生激活/失活对 将比较完好和恢复的LHS和DHS受试者的各种姿势任务的表现。 这项研究将为脊髓损伤引起的脊髓上活动的变化提供独特的信息 神经网络，负责运动缺陷以及潜在的变化 不完全性脊髓损伤受试者的功能恢复。这一信息在临床上是相关的，可以作为 设计新的康复策略以恢复姿势缺陷患者的姿势功能。

Project Summary/Abstract The inability to maintain upright body posture and balance is one of the major motor disorders following spinal cord injury (SCI). In our previous, NIH-supported studies, specific distortions in operation of spinal postural mechanisms (networks) underlying each of three main phenomena related to SCI – spinal shock, the development of spasticity, and the recovery of postural functions have been demonstrated in an animal model (rabbit). We also demonstrated a crucial role of supraspinal postural networks in control of posture. A general goal of the present project is to explain effects of SCI on postural functions on the basis of SCI-caused changes in the operation of the corresponding supraspinal neuronal postural networks. Clinical data suggest that most SCIs are incomplete. Incomplete SCIs cause severe distortions in the interaction between the brain and the spinal cord. This leads to a dramatic decrease or asymmetry of muscle tone and postural limb reflexes resulting in the inability to stand and maintain balance. Our Aim 1 is to analyze the effects of incomplete SCIs (lateral and dorsal hemisection, LHS and DHS) on the operation of supraspinal postural networks, and to explain postural deficits by the changes in the activity of specific ascending and descending pathways. We have developed a novel technique that allows to perform “reversible LHS or DHS” repeatedly many times. This allows studying postural responses and the activity of individual neurons of the ascending and descending pathways under two conditions: (i) when the brain is connected to the spinal cord and (ii) during LHS or DHS, when the connection between the spinal cord and the brain through lateral or dorsal pathways, respectively, is temporarily blocked. Previously we have shown that, after DHS and LHS, postural functions recover in a few weeks. Our Aim 2 is to analyze the activity of supraspinal postural networks in recovered LHS- and DHS- subjects, and to explain the recovery by changes in the activity of specific populations of ascending and descending neurons. For this purpose, we will (i) record the activity of individual neurons of the supraspinal postural networks during postural performance in recovered LHS- and DHS-subjects, and (ii) compare the results with those obtained in intact subjects and in subjects after acute LHS and DHS. Our Aim 3 is to analyze the role of different descending pathways in control of specific aspects of postural behavior in recovered LHS- and DHS-subjects, and to explain the recovery by the changes in the functional role of particular pathways. For this purpose, the effects of the chemogenetic activation/inactivation of different supraspinal pathways on the performance of various postural tasks in intact and recovered LHS- and DHS-subjects will be compared. This study will provide unique information about the SCI-caused changes in the activity of supraspinal neuronal networks, which are responsible for the motor deficits, as well as about the changes underlying functional recovery in subjects with incomplete SCI. This information is clinically relevant as a basis for designing new rehabilitation strategies for recuperating postural functions in patients with postural deficits.