Restoration of postural control after spinal cord injury

描述（由申请人提供）：无法保持直立的身体姿势和平衡是创伤性脊髓损伤（SCI）后的主要运动障碍之一。在我们之前由nih支持的研究中，我们在动物模型（兔）中对脊髓损伤后的姿势功能损伤和恢复进行了表征。本项目的总体目标是在sci引起的相应神经元姿势机制（网络）操作变化的基础上解释这些现象。完全性脊髓损伤消除了大脑对脊髓的所有影响，从而导致脊髓休克（肌肉张力和脊髓反射急剧下降）。我们的目的1是分析完全性脊髓损伤对脊柱体位网络运作的影响，并通过特定脊髓神经元群活动的变化来解释脊髓休克。我们开发了一种新的技术来研究脊髓休克的神经元机制。在T12处冷却脊髓会暂时阻断脊髓通路中的信号传递——“可逆脊髓化”，这可以重复多次。这允许在两种情况下研究个体脊髓神经元的姿势反应和活动：(i)当脊髓与大脑连接时，以及（ii）脊髓休克时，当脊髓暂时与大脑断开。脊髓休克后是一段逐渐发展为痉挛的时期（包括反射反应异常、耳鸣和张力增高）。我们的目的2是分析这一时期脊柱体位网络的活动，并通过特定脊髓神经元群活动的变化来解释痉挛的不同方面的发展。为此，我们将(i)记录痉挛不同阶段单个脊髓神经元的姿势反射和活动，以及（ii）将神经元活动的变化与姿势表现的变化联系起来。先前我们已经证明，在不完全性脊髓损伤（外侧半切）后，姿势功能在几周内恢复。我们的目的3是揭示脊柱和棘上机制的可塑性变化对功能恢复的贡献。这将通过比较不同代偿程度下动物个体脊髓神经元的姿势反射和活动来完成(i)在未损伤侧脊髓通路冷阻断之前和（ii）期间。这项研究将提供关于脊髓损伤引起的脊髓神经元网络活动变化的独特信息，脊髓神经元网络活动变化是导致运动缺陷的原因，以及不完全性脊髓损伤受试者功能恢复的潜在变化。这一信息作为设计新的脊髓损伤患者康复策略的基础具有临床意义。这些策略可以专注于恢复特定脊髓神经元群的正常活动。

DESCRIPTION (provided by applicant): Inability to maintain upright body posture and equilibrium is one of the major motor disorders following traumatic spinal cord injury (SCI). In our previous, NIH-supported studies, impairment and recovery of postural functions after SCI were characterized in an animal model (rabbit). A general goal of the present project is to explain these phenomena on the basis of SCI-caused changes in the operation of the corresponding neuronal postural mechanisms (networks). Complete SCI abolishes all brain influences on the spinal cord, which results in spinal shock (a dramatic decrease of muscle tone and spinal reflexes). Our Aim 1 is to analyze the effect of complete SCI on the operation of spinal postural networks, and to explain spinal shock by the changes in activity of specific groups of spinal neurons. We have developed a novel technique for studying neuronal mechanisms of spinal shock. Cooling the spinal cord at T12 causes a temporary blockade of signal transmission in spinal pathways - "reversible spinalization", which can be done repeatedly many times. This allows studying postural responses and activity of individual spinal neurons under two conditions: (i) when the spinal cord is connected with the brain, and (ii) during spinal shock, when the spinal cord is temporarily disconnected from the brain. Spinal shock is followed by a period of gradually developing spasticity (including abnormal reflex responsiveness, clonus, and hypertonus). Our Aim 2 is to analyze activity of spinal postural networks during this period, and to explain the development of different aspects of spasticity by the changes in activity of specific groups of spinal neurons. For this purpose, we will (i) record postural reflexes and activity of individual spinal neurons at different stages of spasticity, and (ii) correlate the changes in neuronal activity with the changes in postural performance. Previously we have shown that, after incomplete SCI (lateral hemisection), postural functions recover in a few weeks. Our Aim 3 is to reveal the contribution of plastic changes in the spinal and supraspinal mechanisms to functional recovery. This will be done by comparing postural reflexes and activity of individual spinal neurons in animals at different degrees of compensation (i) before and (ii) during the cold block of spinal pathways on the undamaged side. This study will provide unique information about the SCI-caused changes in the activity of spinal 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 in SCI subjects. These strategies can be focused on restoration of normal activity in specific groups of spinal neurons.