Lotfi Parisa, Garde Kshitija, Chouhan Amit K, Bengali Ebrahim, Romero-Ortega Mario I
Department of Bioengineering, University of Texas at Arlington Arlington, TX, USA.
Front Neuroeng. 2011 Oct 12;4:11. doi: 10.3389/fneng.2011.00011. eCollection 2011.
Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed sub-modality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF) and neurotrophin-3 (NT-3), to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5-fold compared to that in saline or NT-3, whereas the number of branches increased threefold in the NT-3 channels. These results were confirmed using a 3D "Y"-shaped in vitro assay showing that the arm containing NGF was able to entice a fivefold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a "Y"-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted toward the sural nerve, while N-52+ large-diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.
再生性周围神经接口已被提议作为机器人假肢自然控制的可行替代方案。然而，神经接口处的感觉和运动轴突具有混合的亚模态类型，这使得从运动轴突进行特定记录以及通过选择性刺激引出精确的感觉模态变得困难。在这里，我们评估了使用特定类型的神经营养因子来优先吸引横断的周围神经中特定轴突群体再生到不同隔室的可能性。通过神经生长因子（NGF）和神经营养因子-3（NT-3）的分隔扩散递送，在体外评估了背根神经节神经元混合感觉纤维的分离，以分别优先吸引感觉神经元的TrkA+伤害性感受和TrkC+本体感受亚群的生长。与盐水或NT-3相比，NGF通道中的平均轴突长度增加了2.5倍，而NT-3通道中的分支数量增加了三倍。使用3D“Y”形体外试验证实了这些结果，该试验表明含有NGF的臂能够使无分支纤维的轴突长度增加五倍。为了研究这种分离是否能在体内被诱导，使用了一个“Y”形管道，以使成年大鼠横断的坐骨神经再生到分别填充有NFG或NT-3的不同隔室中。大量CGRP+疼痛纤维被吸引到腓肠神经，而在胫神经和NT-3隔室中观察到N-52+大直径轴突。这项研究证明了在特定再生腔室中感觉轴突的引导性富集，并支持了神经营养因子可用于在不同的周围接口中分离感觉轴突甚至运动轴突的观点。
