Identifying novel trunk reflexes and their differences after neonatal versus adult spinal cord injury

新生儿与成人脊髓损伤后识别新的躯干反射及其差异

• 批准号: 10753793
• 负责人: SIMON F GISZTER
• 金额: $ 41.19万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753793
• 关键词: Adolescent; Adult; Anatomy; Animal Model; Bilateral; Biomechanics; Categories; Chest; Cholera Toxin; Clinic; Contralateral; Coupling; Data; Dendrites; Electrophysiology (science); Elements; Equilibrium; Felis catus; Fractionation; Future; Generations; Goals; H-Reflex; Hindlimb; Individual; Injury; Interneurons; Lesion; Literature; Locomotion; Locomotor Recovery; Medial; Methods; Motion; Motor; Motor Neurons; Mus; Muscle; Natural regeneration; Neonatal; Neurotransmitters; Pathway interactions; Pattern; Physiological; Population; Publishing; Rattus; Recovery; Recovery of Function; Reflex action; Rehabilitation therapy; Reporting; Research; Rodent; Rodent Model; Role; Spinal; Spinal cord injury; Structure; Synapses; Testing; Time; Variant; Vertebral column; Weight; Weight-Bearing state; Work; anatomical tracing; design; high reward; high risk; improved; injured; insight; mad itch virus; mature animal; monosynaptic reflex; motor control; motor function recovery; neonatal injury; neonate; novel; novel therapeutics; rehabilitation strategy; repaired; response; restoration; spinal reflex; synergism; translational potential

Project Summary / Abstract A highly compelling observation in spinal cord injury (SCI) is that in neonatal complete spinal transection at thoracic levels in cats, rats and mice, a fraction of the injured individuals develop variations of useful quadrupedal weight-supported locomotion as adults, although after complete spinal transection in adult animals there is no useful recovery. In rats the fraction of individuals that show integrated quadrupedal weight support, using the hindlimbs is about 20%. Understanding how this level of function is developed after neonatal spinal complete injury and maintained in adults may be an important signpost to new therapies applicable in clinic. We and others have published data indicating that trunk control is crucial to the useful quadrupedal weight- supported locomotion of neonatal injured rats. New data in our group suggested some previously undescribed monosynaptic contralateral reflex pathways in the rat trunk. These reflexes couple muscles across the midline with rapid reflexes. Other published data shows that alteration in trunk motoneuron structure in early neonate SCI which might alter these newly discovered pathways, which would impact trunk control. This speculated difference might be among mechanisms that support the unusually good recovery of quadrupedal function after neonatal SCI. Our goals in the proposed project are to test if the trunk reflex patterns seen in adult animals are altered after spinal cord injury, focusing on the novel contralateral monosynaptic pathways. We hypothesize that after neonatal SCI the novel contralateral monosynaptic pathways are lost. We test this with two Specific Aims, the first examining the hypothesis using anatomical tracing, and the second using electrophysiological reflex testing. The significance of the project is that the data to be obtained will lead to better understanding of elements of trunk motor function, and recovery of trunk motor function after SCI. The data will determine future directions of research in neonatal and adult SCI in rodent models. Trunk control and recovery of effective trunk control is a crucial aspect of the restoration and recovery of motor function after both adult, juvenile and neonatal SCI. Depending on the results, the project data may lead to the design of new therapies and tests in rodents, with potential for translation to clinic.

项目摘要/摘要 脊髓损伤(SCI)的一个非常令人信服的观察是新生儿完全性脊髓横断。 在猫、大鼠和小鼠的胸部水平上，一小部分受伤的个体产生了有用的四足动物的变异 成年动物的负重运动，尽管在成年动物的完全脊髓横断后没有 有用的恢复。在大鼠中，表现出整合的四足重量支持的个体的比例，使用 后肢约为20%。了解新生儿脊柱完整后这种水平的功能是如何发展的 在成人中的损伤和维持可能是临床应用新疗法的一个重要标志。 我们和其他人发表的数据表明，躯干控制对有用的四足动物体重至关重要- 支持新生损伤大鼠的活动。我们小组的新数据表明，一些以前没有描述过的数据 大鼠躯干的单突触对侧反射通路。这些反射连接着中线上的肌肉。 具有快速反应能力。其他已发表的数据表明，新生儿早期躯干运动神经元结构的变化 脊髓损伤可能会改变这些新发现的通路，从而影响躯干控制。这是在推测 不同的机制可能是支持四足动物功能异常良好的恢复 新生儿脊髓损伤。我们在提议的项目中的目标是测试成年动物的躯干反射模式是否 脊髓损伤后改变，集中在新的对侧单突触通路上。我们假设 新生儿脊髓损伤后，新的对侧单突触通路丢失。我们有两个明确的目标来测试这一点， 第一种是使用解剖追踪来检验假设，第二种是使用电生理反射 测试。该项目的意义在于，将获得的数据将有助于更好地了解元素 脊髓损伤后躯干运动功能的恢复。这些数据将决定未来的方向 在啮齿动物模型中研究新生儿和成年脊髓损伤。干线控制和恢复有效的干线控制是一种 成人、青少年和新生儿脊髓损伤后运动功能恢复和恢复的关键方面。 根据结果，项目数据可能会导致在啮齿动物身上设计新的治疗方法和测试， 有可能转化为临床。