Reinnervation of Paralyzed Muscle by Nerve-Muscle-Endplate Band Grafting

通过神经-肌肉-终板带移植术恢复瘫痪肌肉的神经

• 批准号: 7596496
• 负责人: LIANCAI MU
• 金额: $ 26.73万
• 依托单位: HACKENSACK UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596496
• 关键词: Anastomosis - action; Animals; Automobile Driving; Axon; Biochemical; Cervical; Data; Denervation; Documentation; Enzymes; Feasibility Studies; Fiber; Future; Glycogen; Goals; Grouping; Harvest; Health Sciences; Healthcare; Horseradish Peroxidase; Implant; Indium; Induction of neuromuscular blockade; Investigation; Label; Lead; Measurement; Methods; Modeling; Morphology; Motor; Motor Endplate; Motor Neurons; Movement; Muscle; Muscle Fibers; Muscle denervation procedure; Muscle rehabilitation; Myosin Heavy Chains; Natural regeneration; Nerve; Nerve Endings; Neuromuscular Diseases; Neuromuscular Junction; Operative Surgical Procedures; Outcome; Paralysed; Patients; Peripheral nerve injury; Pilot Projects; Procedures; Rate; Rattus; Recovery of Function; Research; Research Design; Site; Skeletal Muscle; Solutions; Source; Sternocleidomastoid Muscle; Techniques; Testing; Time; Transplantation; Work; axon regeneration; base; clinical application; design; feeding; functional restoration; implantation; improved; nervous system disorder; novel strategies; prevent; reinnervation; relating to nervous system; repaired; restoration; size; success

DESCRIPTION (provided by applicant): Neuromuscular denervation is a common consequence of peripheral nerve injuries and neurological diseases. There is a pressing need to seek novel approaches of reinnervation for restoration of paralyzed muscles as the presently used methods generally result in poor functional recovery. The global hypothesis driving this project is that better outcomes could be achieved by reinnervating a paralyzed muscle with an abundant source of intact nerve terminals and motor endplates. This idea promoted us to develop a nerve- muscle-endplate band grafting (NMEG) method to reinnervate paralyzed muscles. Cervical strap muscles were selected to perform feasibility studies in a rat model. The NMEG was harvested from the omohyoid (OH) muscle and then transplanted to the experimentally paralyzed sternomastoid (SM) muscle. Meanwhile, nerve- muscle pedicle (NMP) and end-to-end anastomosis (EEA) reinnervation procedures were also carried out for comparison. Our pilot studies using immediate reinnervation model showed that NMEG resulted in successful neuroregeneration and better functional recovery than the NMP and EEA. This research is to determine the efficacy of the NMEG for the immediate and delayed reinnervation of paralyzed cervical strap muscles as compared with the classic EEA technique. Studies designed in this proposal will document the fundamental neural basis of the functional recovery and other major factors influencing outcomes. We hypothesized that the extent of functional recovery of a reinnervated muscle is largely dependent on both the quantity of the reestablished nerve-muscle contacts and the denervation induced muscular alterations and that the NMEG would be a better option for muscle reinnervation than the commonly used EEA and other methods. These hypotheses will be tested with the following 3 specific aims. Specific Aim 1 is to evaluate functional recovery of the reinnervated muscles by analyzing electromyographic (EMG) recordings, muscle force and movement measurements, and distribution of the glycogen depleted muscle fibers. Specific Aim 2 is to demonstrate the neural basis of the functional restoration of the reinnervated muscles by quantifying the retrograde horseradish peroxidase (HRP) labeled motoneurons, regenerating axons and sprouts, and newly formed motor endplates. Specific Aim 3 is to explore procedure-related and time-dependent morphological, immunocytochemical, and biochemical changes in the reinnervated muscles by analyzing muscle mass, fiber size, fiber type grouping, and fiber type and myosin heavy chain (MHC) composition. The results will allow the reliable documentation of the efficacy of the NMEG in rehabilitation of muscle paralysis. The significance of the proposed work extends far beyond what is currently understood. Once the advantages of the NMEG are fully documented by extensive animal studies, the impact of this research on science and health care could be substantial as the data obtained from this research are useful for ultimate clinical application in the near future to the treatment of patients with paralytic neuromuscular disorders. As an entirely satisfactory solution to restoration of the paralyzed skeletal muscles has not yet been found, we developed a new technique (nerve-muscle-endplate band grafting) to reinnervate paralyzed cervical strap muscles in a rat model. Our preliminary work showed that this technique results in better outcomes than currently used methods. The data obtained from this research is useful for future clinical application to treat muscle paralysis.

描述（由申请人提供）：神经肌肉神经神经是周围神经损伤和神经系统疾病的普遍结果。由于目前使用的方法通常会导致功能恢复不良，因此需要寻求新的重新支配方法来恢复瘫痪的肌肉。推动该项目的全球假设是，可以通过重新构造具有丰富的完整神经末端和运动终结来源的瘫痪肌肉来实现更好的结果。这个想法促进了我们开发一种神经肌肉式板带移植（NMEG）方法来重新弥补瘫痪的肌肉。选择宫颈皮带肌肉以在大鼠模型中进行可行性研究。将NMEG从Omhyoid（OH）肌肉中收获，然后移植到实验性瘫痪的胸骨类动物（SM）肌肉中。同时，还进行了神经肌椎弓根（NMP）和端到端吻合术（EEA）重新支配程序进行比较。我们使用立即重新支配模型的初步研究表明，与NMP和EEA相比，NMEG导致了成功的神经创造和更好的功能恢复。这项研究是为了确定NMEG与经典EEA技术相比，NMEG对瘫痪的宫颈皮带肌肉的立即和延迟加剧的功效。该提案中设计的研究将记录功能恢复的基本神经基础和其他影响结果的主要因素。我们假设，重新染色的肌肉功能恢复的程度在很大程度上取决于重建的神经肌肉接触的数量和去神经肌的肌肉改变，而NMEG将是与常用EEA和其他EEA和其他方法相比，NMEG将是肌肉重新连接的更好选择。这些假设将通过以下3个特定目标进行检验。具体目的1是通过分析肌电图（EMG）记录，肌肉力和运动测量以及糖原耗尽的肌肉纤维的分布来评估重新启动的肌肉的功能恢复。具体目的2是通过量化标记运动神经元，再生轴突和新芽的逆行辣根过氧化物酶（HRP），以及新形成的运动端层来证明重新启动肌肉功能恢复的神经基础。具体目的3是通过分析肌肉质量，纤维大小，纤维类型，纤维类型和肌球蛋白重链（MHC）组成，探索与时间相关的和时间有关的形态，免疫细胞化学和生化变化。结果将允许对NMEG恢复肌肉瘫痪的疗效的可靠记录。拟议工作的重要性远远超出了当前所理解的范围。一旦广泛的动物研究充分证明了NMEG的优势，这项研究对科学和医疗保健的影响可能很大，因为从这项研究中获得的数据对于在不久的将来可用于治疗麻痹性神经肌肉疾病的患者的最终临床应用。作为尚未发现瘫痪骨骼肌的完全令人满意的解决方案，我们开发了一种新技术（神经肌肉 - 式板带移植），以重新弥补大鼠模型中瘫痪的宫颈颈肌。我们的初步工作表明，这项技术比目前使用的方法可以取得更好的结果。从这项研究获得的数据对于将来的临床应用来治疗肌肉瘫痪很有用。