Hibbard Emily A, Zhou Liwen, Yang Cathy Z, Venkudusamy Karthik, Montoya Yessenia, Olivarez Alexa, Bittner George D, Sengelaub Dale R
Program in Neuroscience, Indiana University, Bloomington, IN, USA.
Department of Neuroscience, University of Texas at Austin, Austin, TX, USA.
Neural Regen Res. 2025 Jul 1;20(7):2095-2107. doi: 10.4103/NRR.NRR-D-23-01845. Epub 2024 Jun 3.
JOURNAL/nrgr/04.03/01300535-202507000-00030/figure1/v/2024-09-09T124005Z/r/image-tiff Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions; behavioral recovery is typically poor. We used a plasmalemmal fusogen, polyethylene glycol (PEG), to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves. We have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration, and PEG-fused animals exhibit rapid (within 2-6 weeks) and extensive locomotor recovery. Furthermore, our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific, i.e., spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target muscles. In this study, we examined the consequences of PEG-fusion for sensory axons of the sciatic nerve. Young adult male and female rats (Sprague-Dawley) received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without (Negative Control) the application of PEG. Compound action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury site. The success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days postoperatively. At 2-42 days postoperatively, we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish peroxidase. PEG-fusion repair reestablished axonal continuity. Compared to unoperated animals, labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn, as well as inappropriate mediolateral and rostrocaudal areas. Unexpectedly, despite having intact peripheral nerves, similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repair. This central reorganization may contribute to the improved behavioral recovery seen after PEG-fusion repair, supporting the use of this novel repair methodology over currently available treatments.
《期刊》/nrgr/04.03/01300535 - 202507000 - 00030/图1/v/2024 - 09 - 09T124005Z/r/图像 - tiff 周围神经损伤会导致远端神经节段迅速退化，运动和感觉功能立即丧失；行为恢复通常较差。我们使用了一种质膜融合剂聚乙二醇（PEG），立即融合大鼠坐骨神经中切断的近端和远端轴突紧密相邻的开放末端。我们之前报道过，通过PEG融合修复的坐骨神经轴突不会发生华勒氏变性，并且经PEG融合的动物表现出快速（2 - 6周内）且广泛的运动恢复。此外，我们之前的报告显示，切断的坐骨运动轴突的PEG融合是非特异性的，即发现经PEG融合的动物中的脊髓运动神经元投射到合适以及不合适的靶肌肉。在本研究中，我们研究了PEG融合对坐骨神经感觉轴突的影响。年轻成年雄性和雌性大鼠（斯普拉格 - 道利大鼠）接受坐骨神经的单侧单次切断或消融损伤，随后进行有或没有（阴性对照）PEG应用的修复。PEG融合修复后立即记录的复合动作电位证实了跨损伤部位的传导。通过坐骨神经功能指数测试证实了PEG融合的成功，经PEG融合的动物在术后35天开始显示运动功能改善。在术后2 - 42天，我们在双侧皮内注射结合辣根过氧化物酶的小麦胚凝集素后，从后爪背侧对感觉传入神经进行顺行标记。PEG融合修复重建了轴突连续性。与未手术的动物相比，在经PEG融合的动物中，损伤同侧标记的感觉传入神经出现在背角的合适区域以及不合适的内外侧和前后区域。出乎意料的是，尽管周围神经完整，但在损伤和修复的对侧也观察到了标记感觉传入神经的类似重组。这种中枢重组可能有助于解释PEG融合修复后观察到的行为恢复改善，支持在现有治疗方法之上使用这种新型修复方法。
