利用靶向神经移植术重建缺失肢体运动神经信息源及机制研究

Several studies have shown that the residual parts of highly amputated individuals are able to provide sufficient Electromyography (EMG) signal for the efficient control of a multifunctional myoelectric prosthesis. In addition, the EMG signals gotten from the residual part of such individuals’ body makes it difficult to realize their actual motion intention. This project will study how Targeted Nerve Grafting (TNG) technique can be used to improve the limb motor function in animal model. We intend to use Sprague Dawley (SD) Rats as the animal in this study, and graft the rat’s median nerve into its biceps brachii muscle branch of the musculocutaneous nerve to achieve the reconstruction of nerve into muscle to establish the nerve reconstruction in rat model. With the established rat model, the project seeks to study methods for the reconstruction of nerve function and myoelectric information gotten from residual limbs. Also, the change in characteristics of myoelectric signal in the process of rat neural function rehabilitation by implantable electromyography collection, the regeneration and distribution of peripheral nerve in the targeted muscle, and the characteristics of construction mechanics of the targeted muscle will be explored using methods such as histomorphology and physiology. the morphological and functional changes.of synapse in spinal cord and primary somatosensory and motor cortex(S1, M1) will be explored by using electron microscopy and the patch clamp. In addition, the expression of PSD-95-NR2B , synaptophysin in spinal cord, S1 and M1 will be investiagted by icmmunohistochemistry staining, Western blot and immunoprecipitation. These studies will help us to understand the mechanism of.neural plasticity caused by TNG. The mechanism for the limb morot restore, the effect of TNG on peripheral nerve, and the possibility of biological enhancement will be investigated in the project. Lastly, this study will provide theoretical and experimental basis for the clinical application of TNG.

针对高位截肢者残存肢体肌肉有限，不能为多自由度假肢的肌电控制提供足够肌电信息源，难以实现运动意图在精确识别，本项目利用靶向神经移植技术（TNG）与动物模型，研究重建截肢后残存肢体运动功能的方法，为假肢控制提供更多的肌电信息。本项目拟以大鼠为研究对象，将大鼠正中神经近侧端与支配肱二头肌的神经肌支吻合，实现正中神经在肱二头肌中的重建，建立大鼠模型。利用动物行为学与在体肌电采集，评价肢体运动神经功能重建效果及肌电信号变化特点；利用组织形态学与生理学方法，研究神经在肌肉中的再生与分布情况及肌肉的收缩特性；利用高尔基染色、电镜和膜片钳技术，研究TNG对脊髓和脑皮质S1、M1区内突触形态及功能可塑性的影响； 利用免疫组化、Western blot及免疫沉淀技术，研究突触相关蛋白及PSD95-NR2B在脊髓和S1、M1区中的表达，阐明其机制，为临床应用提供提供理论和实验依据。

针对高位截肢者残存肢体肌肉有限，不能为多自由度假肢的肌电控制提供足够肌电信息源，难以实现运动意图在精确识别，本项目利用靶向神经移植技术（TNG）与动物模型，研究重建截肢后残存肢体运动功能的方法，期望为假肢控制提供更多的肌电信息。本项目已利用靶向神经移植技术(Targeted Nerve Grafting, TNG)建立大鼠模型，使用神经生理学、动物行为学及神经形态学研究方法，探索了TNG技术重建大鼠肢体运动功能的效果及重建机理，建立了大鼠后肢靶向肌肉神经移植模型，研究了外周神经（臂丛与骶丛的神经分支支）横断小鼠后肢运动功能和肌肉萎缩的形态学特征；本项目发现靶向肌肉神经移植技术可以增加肢体外周神经（胫神经）的轴突数量和髓鞘厚度，增强了脊髓前角运动神经元和脊髓运动神经元标志物胆碱乙酰转移酶阳性细胞的数量及突触可塑性相关的突触素免疫荧光强度；研究结果表明，靶向神经移植技术(TNG)技术可有效地利用肢体原有靶向神经的神经网络，重建肢体运动功能，缩短了神经重建后的康复时间，增强了失神经后神经功能重建的康复效果，使得失神经肌肉的运动功能得到了恢复，并为后续的靶向神经功能重建研究提供了可靠的的TNG动物模型。