聚乙二醇融合修复切断的大鼠坐骨神经,重建轴突连续性并重组脊髓感觉末梢场。

IF 5.9 2区 医学 Q2 CELL BIOLOGY Neural Regeneration Research Pub Date : 2025-07-01 Epub Date: 2024-06-03 DOI:10.4103/NRR.NRR-D-23-01845
Emily A Hibbard, Liwen Zhou, Cathy Z Yang, Karthik Venkudusamy, Yessenia Montoya, Alexa Olivarez, George D Bittner, Dale R Sengelaub
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引用次数: 0

摘要

摘要:周围神经损伤导致远端神经节段迅速变性,并立即丧失运动和感觉功能;行为恢复通常很差。我们使用一种质膜融合剂聚乙二醇(PEG)来立即融合大鼠坐骨神经中被切断的近端和远端轴突紧密贴合的开口端。我们以前曾报道过,通过 PEG 融合修复的坐骨神经轴突不会发生 Wallerian 退化,而且 PEG 融合的动物表现出快速(2-6 周内)和广泛的运动恢复。此外,我们之前的报告显示,PEG 融合断裂的坐骨神经运动轴突是非特异性的,即发现 PEG 融合动物的脊髓运动神经元可投射到适当和不适当的靶肌肉。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。年轻的成年雄性和雌性大鼠(Sprague-Dawley)接受了单侧坐骨神经单切或消融损伤,随后在应用或不应用 PEG(阴性对照)的情况下进行了修复。PEG 融合修复后立即记录的复合动作电位证实了损伤部位的传导。通过坐骨神经功能指数测试证实了 PEG 融合的成功,术后 35 天开始,PEG 融合动物的运动功能有所改善。术后 2-42 天,我们在双侧皮内注射小麦胚芽凝集素共轭辣根过氧化物酶后,对后爪背侧的感觉传入进行了逆行标记。PEG融合修复重建了轴突的连续性。与未手术的动物相比,PEG融合动物损伤同侧的背角适当区域以及不适当的内外侧和喙尾区域都发现了标记的感觉传入。意想不到的是,尽管外周神经完好无损,但在损伤和修复的对侧也观察到了类似的标记感觉传入重组。这种中枢重组可能是 PEG 融合修复术后行为恢复得到改善的原因之一,支持使用这种新颖的修复方法,而不是目前可用的治疗方法。
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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord.

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.

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来源期刊
Neural Regeneration Research
Neural Regeneration Research CELL BIOLOGY-NEUROSCIENCES
CiteScore
8.00
自引率
9.80%
发文量
515
审稿时长
1.0 months
期刊介绍: Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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