Gloviczki Balázs, Török Dénes G, Márton Gábor, Gál László, Bodzay Tamás, Pintér Sándor, Nógrádi Antal
1 Laboratory of Neural Regeneration, Department of Anatomy, Histology, and Embryology, University of Szeged , Szeged, Hungary .
2 Department of Traumatology, Sándor Péterfy Hospital , Budapest, Hungary .
J Neurotrauma. 2017 Aug 1;34(15):2364-2374. doi: 10.1089/neu.2016.4754. Epub 2017 Jun 28.
Ventral root avulsion induces dramatic loss of the affected spinal cord motoneurons. The neuroprotective effect of riluzole has been previously proven on the injured motoneurons: the vast majority of them can be rescued even when they have no possibility to regenerate their axons. In this study the number of injured motoneurons rescued by riluzole treatment and their capacity to reinnervate the denervated forelimb muscles was investigated. Surgical reconnection with a peripheral nerve graft between the affected spinal cord segment and the C7 spinal nerve was established immediately or with 1- and 3-week delay after avulsion. Avulsion and immediate reconnection of the motoneuron pool to the spinal nerve resulted in moderate reinnervation of the spinal nerve (281 ± 23 standard error of mean [SEM] retrogradely labeled motoneurons), whereas treatment of the injured motoneurons with riluzole yielded considerably higher numbers of reinnervating motoneurons (548 ± 18 SEM). Reconnection of the motor pool with the C7 spinal nerve with 1-week delay allowed fewer motor axons to reinnervate their targets in control and riluzole-treated animals (159 ± 21 vs. 395 ± 16 SEM). A clinically relevant 3-week delay in reconnection further reduced the number of reinnervating motoneurons (76 ± 22 SEM), but riluzole pre-treatment still enabled a significant number of rescued motoneurons (396 ± 17 SEM) to regenerate their axons into the C7 spinal nerve. These results show that those injured adult motoneurons that are rescued by riluzole treatment started immediately after the avulsion injury are able to reinnervate their targets even if they are provided with a conduit several weeks after the primary injury. This finding suggests that partial rescue of injured motoneurons with riluzole in patients who suffered a brachial plexus avulsion injury may provide an available pool of surviving motoneurons for late reconnection/reimplantation surgeries.
腹根撕脱会导致受影响的脊髓运动神经元大量丧失。利鲁唑对受损运动神经元的神经保护作用此前已得到证实:即使绝大多数运动神经元无法再生其轴突,它们中的绝大多数仍可被挽救。在本研究中,研究了利鲁唑治疗挽救的受损运动神经元数量及其重新支配失神经支配的前肢肌肉的能力。在撕脱后立即或延迟1周和3周后,通过外周神经移植在受影响的脊髓节段和C7脊神经之间建立手术再连接。运动神经元池与脊神经的撕脱和立即再连接导致脊神经的适度再支配(平均[SEM]逆行标记运动神经元为281±23),而用利鲁唑治疗受损运动神经元产生的再支配运动神经元数量要高得多(548±18 SEM)。延迟1周将运动神经元池与C7脊神经重新连接,使得在对照和利鲁唑治疗的动物中,较少的运动轴突能够重新支配其靶标(159±21与395±16 SEM)。临床上相关的3周延迟再连接进一步减少了再支配运动神经元的数量(76±22 SEM),但利鲁唑预处理仍使大量被挽救的运动神经元(396±17 SEM)能够将其轴突再生到C7脊神经中。这些结果表明,那些在撕脱伤后立即接受利鲁唑治疗而被挽救的成年受损运动神经元,即使在原发性损伤数周后才提供导管,也能够重新支配其靶标。这一发现表明,在臂丛神经撕脱伤患者中,用利鲁唑部分挽救受损运动神经元可能为后期的重新连接/再植入手术提供一批存活的运动神经元。