Franz Colin K, Rutishauser Urs, Rafuse Victor F
Department of Anatomy and Neurobiology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5.
Brain. 2008 Jun;131(Pt 6):1492-505. doi: 10.1093/brain/awn039. Epub 2008 Mar 11.
Despite advances in microsurgical techniques, recovery of motor function after peripheral nerve injury is often poor because many regenerating axons reinnervate inappropriate targets. Consequently, surgical repair must include treatment strategies that improve motor axon targeting. Development of such treatments will require a better understanding of the molecular mechanisms governing selective motor axon targeting. This study used a well-established model of nerve transection and repair to examine (1) whether intrinsic differences exist between different pools of motoneurons after peripheral nerve injury, (2) if such differences regulate selective axon targeting, (3) if regenerating motor axons must express polysialic acid (PSA) in order to preferentially reinnervate muscle and (4) whether brief electrical stimulation improves regeneration accuracy because it increases PSA expression on regenerating axons. We found that different motor pools differentially express PSA after injury and that the capacity to re-express PSA appears to be an intrinsic neuronal property established during development. Second, motoneuron pools not up-regulating PSA did not preferentially reinnervate muscle after injury. Third, brief electrical stimulation of the proximal nerve stump immediately after injury only improved selective motor axon targeting if the motoneurons were capable of up-regulating PSA. Finally, the benefits of stimulation were completely abolished if PSA was removed from the regenerating axons. These results indicate that (1) intrinsic neuronal differences between motor pools must be considered in the development of treatments designed to improve axon targeting and (2) therapeutics aimed at increasing PSA levels on regenerating motor axons may lead to superior functional outcomes.
尽管显微外科技术取得了进展，但周围神经损伤后运动功能的恢复往往很差，因为许多再生轴突会重新支配不适当的靶点。因此，手术修复必须包括改善运动轴突靶向的治疗策略。开发此类治疗方法需要更好地理解控制选择性运动轴突靶向的分子机制。本研究使用了一个成熟的神经横断和修复模型来研究：（1）周围神经损伤后不同运动神经元池之间是否存在内在差异；（2）这些差异是否调节选择性轴突靶向；（3）再生运动轴突是否必须表达多唾液酸（PSA）才能优先重新支配肌肉；（4）短暂电刺激是否能提高再生准确性，因为它会增加再生轴突上的PSA表达。我们发现，损伤后不同的运动神经元池差异表达PSA，重新表达PSA的能力似乎是发育过程中确立的一种内在神经元特性。其次，未上调PSA的运动神经元池在损伤后不会优先重新支配肌肉。第三，损伤后立即对近端神经残端进行短暂电刺激，只有在运动神经元能够上调PSA的情况下，才会改善选择性运动轴突靶向。最后，如果从再生轴突中去除PSA，刺激的益处就会完全消失。这些结果表明：（1）在设计旨在改善轴突靶向的治疗方法时，必须考虑运动神经元池之间的内在神经元差异；（2）旨在提高再生运动轴突上PSA水平的治疗方法可能会带来更好的功能结果。
