Restoration of postural control after spinal cord injury

描述(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。在我们之前的NIH支持的研究中，脊髓损伤后姿势功能的损害和恢复是以动物模型(兔)为特征的。本项目的一个总体目标是根据脊髓损伤引起的相应神经元姿势机制(网络)运行的变化来解释这些现象。完全性脊髓损伤消除了所有大脑对脊髓的影响，导致脊髓休克(肌肉张力和脊髓反射急剧下降)。我们的目的一是分析完全性脊髓损伤对脊髓姿势网络运行的影响，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机制。在T12给脊髓降温会导致脊髓通路信号传递暂时受阻--“可逆棘化”，这可能会重复多次。这使得研究在两种情况下单个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)在脊髓休克期间，当脊髓与大脑暂时断开连接时。脊髓休克之后是一段逐渐发展为痉挛的时期(包括反射反应异常、阵挛和高张力)。我们的目标2是分析脊髓姿势网络在这一时期的活动，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。以前我们已经证明，在不完全SCI(侧半切)后，姿势功能在几周内恢复。我们的目标3是揭示脊柱和脊柱上机制的可塑性变化对功能恢复的贡献。这将通过比较动物在不同代偿程度(I)之前和(Ii)未受损侧脊髓通路冷阻断期间的姿势反射和单个脊髓神经元的活动来完成。这项研究将提供有关脊髓损伤引起的脊髓神经网络活性变化的独特信息，这些变化是导致运动障碍的原因，以及不完全脊髓损伤受试者潜在的功能恢复的变化。这一信息具有临床意义，可作为设计新的脊髓损伤患者康复策略的基础。这些策略可以专注于恢复特定脊髓神经元组的正常活动。

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.