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