Repair of Brachial Sensory Root Injuries in the Spinal Cord

脊髓肱感觉根损伤的修复

• 批准号: 7573790
• 负责人: ERIC FRANK
• 金额: $ 42.86万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7573790
• 关键词: Accidents; Adult; Afferent Neurons; Aftercare; Axon; Back; Behavioral; Boxing; Brachial plexus structure; Code; Crush Injury; Data; Dose; Effectiveness; Family; Fiber; Goals; Hand functions; Human; Injury; Knowledge; Laboratories; Leg; Life; Limb structure; Measures; Methods; Modeling; Motor; Multiple Trauma; Natural regeneration; Nerve; Nociception; Pathway interactions; Peripheral Nerves; Persons; Phase III Clinical Trials; Plant Roots; Proteins; Rattus; Recovery; Reporting; Sensory; Sensory Ganglia; Serum; Specificity; Spinal Cord; Spinal nerve root structure; Synapses; Techniques; Testing; Therapeutic Agents; Treatment Protocols; Upper Extremity; Upper arm; afferent nerve; design; disability; effective therapy; falls; functional improvement; human embryonic stem cell; human subject; improved; injured; member; neurotrophic factor; public health relevance; receptor; repaired; research clinical testing; research study; spinal nerve posterior root

Injuries to the brachial plexus result in the reduction or loss of use of the upper extremities due to damage to the brachial nerves and/or spinal roots. These injuries are usually the result of vehicle accidents or falls. Peripheral nerve grafts have been increasingly effective in restoring some motor and sensory function when only peripheral nerves are damaged or broken. Repair of damaged spinal roots is less successful, however, especially in restoring sensory function after damage or avulsion (breakage) of dorsal roots, which are the pathway of sensory axons from the periphery to the spinal cord. Sensory axons can regenerate within the root itself but do not cross into the spinal cord. When sensory input from the limb is drastically reduced or eliminated in this way, there are life-long disabilities for the injured person. The experiments proposed in this application are designed to develop potential therapies to restore sensory function after damage to dorsal roots. Several neurotrophic factors are already known to promote anatomical and functional regeneration of sensory fibers after dorsal root crush. Artemin, a member of the glial-derived neurotrophic factor family of neurotrophins, is especially effective in promoting the functional regeneration of both large, proprioceptive and small, nociceptive sensory axons after root crush. Artemin will be tested for its ability to restore specific and persistent sensory function following crush injuries of brachial dorsal roots in adult rats. Recovery of sensory function will be assessed using anatomical, behavioral and electrophysiological techniques. In a related project, a method for promoting regeneration after dorsal root avulsion will be developed. Many brachial root injuries result in complete breakage of the roots from the spinal cord (avulsions) rather than partial damage. In these cases, sensory axons must be guided back to the spinal cord before regeneration can occur. The cut ends of avulsed sensory roots will be surgically reattached to the spinal cord and treated with artemin to determine if sensory function can be restored. The goal of these experiments is to determine if artemin is sufficiently effective to warrant study for the repair of brachial root injuries in humans.

臂丛神经损伤会导致上肢功能的减少或丧失，这是由于臂丛神经和/或脊神经根的损伤。这些损伤通常是车祸或福尔斯坠落造成的。当只有周围神经受损或断裂时，周围神经移植物在恢复某些运动和感觉功能方面越来越有效。然而，受损脊神经根的修复不太成功，特别是在背根损伤或撕脱（断裂）后恢复感觉功能，背根是感觉轴突从外周到脊髓的通路。感觉轴突可以在根本身内再生，但不会穿过脊髓。当来自肢体的感觉输入以这种方式急剧减少或消除时，受伤者将终生残疾。 本申请中提出的实验旨在开发潜在的治疗方法，以恢复背根损伤后的感觉功能。已知几种神经营养因子可促进背根挤压后感觉纤维的解剖和功能再生。Artemin是神经营养素的胶质源性神经营养因子家族的成员，在促进根部挤压后大的本体感受和小的伤害感受感觉轴突的功能再生方面特别有效。将测试Artemin在成年大鼠臂背根挤压损伤后恢复特异性和持久感觉功能的能力。将使用解剖学、行为学和电生理学技术评估感觉功能的恢复。在一个相关的项目中，将开发一种促进背根撕脱后再生的方法。许多臂丛神经根损伤导致神经根从脊髓完全断裂（撕脱），而不是部分损伤。在这些情况下，感觉轴突必须在再生发生之前被引导回到脊髓。感觉根撕脱的切断端将通过手术重新连接到脊髓上，并用artemin治疗，以确定感觉功能是否可以恢复。这些实验的目的是确定artemin是否足够有效，以保证研究修复人类肱神经根损伤。