Restoration of postural control after spinal cord injury

描述（由申请人提供）：1)保持基本的身体姿势——人类直立，四足动物背侧朝上——是一项重要的运动功能。有效地控制这个姿势对站立、行走和提供自主运动的支持都很重要。脊髓损伤（SCI）引起的脊髓通路损伤导致体位系统的严重损害。姿势控制的恢复是其他运动功能恢复的必要前提。本研究旨在描述脊髓损伤对动物（兔）体位系统的影响。它将提供由不同类型的脊髓损伤引起的姿势缺陷的数据。(2)脊髓损伤减少或消除脊髓体位网的棘上兴奋驱动。我们的目标是重新激活这个网络，恢复脊柱的姿势反射。这可以通过电刺激或药物刺激脊髓损伤以下的脊髓来实现。我们将测试刺激在脊髓损伤不同阶段的效果。这些实验将为了解脊柱姿势反射损伤的本质提供重要的见解，并将表征其在脊髓损伤进行性阶段的恢复潜力。(3)对脊髓损伤受试者进行步行或负重训练可改善这些运动功能。我们的目的是专门训练姿势系统的两个主要组成部分——负责维持肢体/躯干结构的机制，以及产生姿势反射反应的机制。这些实验将揭示脊髓损伤进行性阶段的最佳训练策略，并为人类受试者的康复提供建议。(4)脊髓损伤急性期取决于多种因素。我们的目的是阐明这些因素之一——脊髓通路信号传递的终止对体位系统活动的影响。这将通过冷却引起的脊髓通路失活（可逆脊髓化）来实现。这些实验将有助于深入了解下行指令在脊髓体位机制激活中的作用，以及脊髓损伤后体位功能障碍的本质。

DESCRIPTION (provided by applicant): 1) Maintenance of the basic body posture - upright in humans and dorsal-side-up in quadrupeds - is a vital motor function. An efficient control of this posture is important for standing, walking, and for providing support of voluntary movements. Damage to spinal pathways caused by the spinal cord injury (SCI) results in a dramatic impairment of the postural system. Restoration of postural control is a necessary prerequisite for the recovery of other motor functions. The proposed study is devoted to characterization of the effects of SCI on the postural system in an animal model (rabbit). It will provide data on postural deficits caused by different types of SCI. (2) The SCI reduces or abolishes the supraspinal excitatory drive to the spinal postural network. Our aim is to re-activate this network and to restore spinal postural reflexes. This will be done by electrical or pharmacological stimulation of the cord below SCI. The efficacy of stimulation at different stages of SCI will be tested. These experiments will provide important insights into the nature of impairments of the spinal postural reflexes, and will characterize their potential for recovery in progressive stages of SCI. (3) Training of stepping or weight bearing in SCI subjects improve these motor functions. Our aim is to train specifically two major components of the postural system - the mechanism responsible for maintenance of limb/trunk configuration, and that generating postural reflex responses. These experiments will reveal optimal strategies for training in progressive stages of SCI, and provide suggestions for rehabilitation in human subjects. (4) The acute stage of SCI depends on many factors. Our aim is to clarify the effect on the activity of postural system produced by one of these factors - the termination of signal transmission in spinal pathways. This will be done by inactivation of spinal pathways caused by their cooling (reversible spinalization). These experiments will provide insights into the role of descending commands for activation of spinal postural mechanisms, and into the nature of postural dysfunction after SCI.