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）的高度令人信服的观察结果是，在新生儿完整的脊柱横断 猫，大鼠和小鼠的胸腔水平，受伤个体的一小部分会出现有用的四足动物的变化 体重支持的运动为成年人，尽管成年动物完全脊柱横断后，没有 有用的恢复。在大鼠中，使用综合体重支持的个体的比例 后肢约为20％。了解新生儿脊柱完成后如何发展这种功能水平 成人的伤害和维持的可能是适用于诊所的新疗法的重要路标。 我们和其他人已经发布了数据，表明躯干控制对于有用的四足体重至关重要 新生儿受伤的大鼠的支撑运动。我们小组中的新数据提出了一些以前未描述的 大鼠躯干中的单突触对侧反射途径。这些反射在整个中线上夫妇肌肉 具有快速反射。其他已发表的数据表明，新生儿早期的树干运动神经元结构的变化 SCI可能会改变这些新发现的途径，从而影响躯干控制。这个推测 差异可能是支持四足动物功能异常恢复的机制之一 新生儿科学。我们在拟议项目中的目标是测试成年动物中看到的躯干反射模式是否是 脊髓损伤后发生了改变，重点是新型对侧单突触途径。我们假设这一点 新生儿SCI后，新型对侧单突触途径丢失了。我们以两个具体目标进行测试， 第一次使用解剖学示踪检查假设，第二个使用电生理反射 测试。该项目的意义在于，要获得的数据将导致更好地理解要素 躯干运动功能和SCI后躯干运动功能的恢复。数据将确定未来的方向 啮齿动物模型中新生儿和成人SCI的研究。行李箱控制和有效躯干控制的恢复是 成人，少年和新生儿科学恢复和恢复运动功能的关键方面。 根据结果​​的不同，项目数据可能会导致啮齿动物的新疗法和测试的设计 转化为诊所的潜力。