Restoration of Postural Control After Spinal Cord Injury

项目总结/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）。在我们以前的NIH支持的研究中，脊柱手术中的特定扭曲 姿势机制（网络）的基础上的三个主要现象与SCI -脊髓休克， 痉挛的发展和姿势功能的恢复已经在动物模型中得到证实 （兔子）。我们还证明了一个至关重要的作用，脊髓上的姿势网络的姿势控制。一般 本项目的目的是在SCI引起的姿势功能的基础上解释SCI对姿势功能的影响。 相应的脊髓上神经元姿势网络的运作变化。临床数据表明 大多数SCI都不完整不完整的SCI会导致大脑和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姿势肢体反射的急剧下降或不对称 导致不能站立和保持平衡。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）对棘上姿势网络操作的影响， 通过特定上行和下行通路活动的变化来解释姿势缺陷。我们 已经开发了一种新的技术，允许执行“可逆的LHS或DHS”重复多次。这 可以研究姿势反应和上行和下行神经元的活动 在两种情况下的路径：（i）当大脑连接到脊髓和（ii）在LHS或DHS期间， 当脊髓和大脑之间分别通过侧向或背侧通路的连接被切断时， 暂时封锁。以前，我们已经表明，DHS和LHS后，姿势功能恢复，在一些 周我们的目的2是分析恢复的LHS-和DHS-患者的脊髓上姿势网络的活动， 受试者，并解释了在特定人群的上升和 下行神经元为此，我们将（i）记录单个神经元的活动， 在恢复的LHS和DHS受试者的姿势表现期间的姿势网络，以及（ii）比较 结果与完整受试者和急性LHS和DHS后受试者的结果一致。目标3：分析 不同的下行通路在控制恢复的LHS中姿势行为的特定方面中的作用， 和DHS的主题，并解释的特定途径的功能作用的变化的恢复。为 为此，我们研究了不同脊髓上途径的化学发生激活/失活对脊髓内神经元的影响。 将比较完整和恢复的LHS和DHS受试者的各种姿势任务的表现。 这项研究将提供关于SCI引起的脊髓上神经活动变化的独特信息。 神经网络，这是负责运动缺陷，以及有关的变化， 不完全SCI患者的功能恢复。该信息具有临床相关性，可作为 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.