The curious ability of polyethylene glycol fusion technologies to restore lost behaviors after nerve severance.
The curious ability of polyethylene glycol fusion technologies to restore lost behaviors after nerve severance.
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DOI：
10.1002/jnr.23685
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发表时间：
2016-03
影响因子：
4.2
通讯作者：
Thayer WP
中科院分区：
文献类型：
--
作者：
Bittner GD;Sengelaub DR;Trevino RC;Peduzzi JD;Mikesh M;Ghergherehchi CL;Schallert T;Thayer WP
PNS和CNS轴突的创伤性损伤并不少见。哺乳动物周围神经轴突（PNA）切断后丧失的行为的恢复依赖于缓慢生长的再生，并且如果在接近索马的消融或损伤之后，则通常很差或不存在。切断脊髓束轴突（STA）后的行为恢复很差，因为STA不能自然再生。目前增强PNA和/或STA再生的技术具有有限的成功，并且不能防止切断的远端节段的沃勒变性的发生。本文介绍了使用最近开发的聚乙二醇（PEG）融合技术相结合的概念，在生物化学工程，细胞生物学和临床显微外科。在显微镜下仔细修剪切割末端并应用明确规定的溶液序列后数分钟内，PEG融合的轴突在整个病变部位表现出形态连续性（通过轴突内染料扩散评估）和电生理连续性（通过动作电位传导评估）。PEG融合的PNA的沃勒变性大大减少，如通过感觉和/或运动轴突的计数以及轴突直径和神经肌肉突触的维持所测量的。在PEG融合修复后，与未处理或常规处理的动物相比，切割或挤压切断或消融的PNA或挤压切断的STA快速（在数天至数周内）、更完全和永久地恢复PNA或STA介导的行为。PEG融合的成功是通过应用抗氧化剂或氧化剂，修剪切断端或拉伸轴突，暴露于无钙或含钙的解决方案，分别增强或减少。PEG融合技术采用临床医生已经使用的外科技术和化学品，并有可能在治疗PNA和STA的创伤性损伤方面产生范式转变。
Traumatic injuries to PNS and CNS axons are not uncommon. Restoration of lost behaviors following severance of mammalian peripheral nerve axons (PNAs) relies on regeneration by slow outgrowths and is typically poor or nonexistent if after ablation or injuries close to the soma. Behavioral recovery after severing spinal tract axons (STAs) is poor because STAs do not naturally regenerate. Current techniques to enhance PNA and/or STA regeneration have had limited success and do not prevent the onset of Wallerian degeneration of severed distal segments. This review describes the use of a recently-developed polyethylene glycol (PEG)-fusion technology combining concepts in biochemical engineering, cell biology and clinical microsurgery. Within minutes after micro-suturing carefully-trimmed cut ends and applying a well-specified sequence of solutions, PEG-fused axons exhibit morphological continuity (assessed by intra-axonal dye diffusion) and electrophysiological continuity (assessed by conduction of action potentials) across the lesion site. Wallerian degeneration of PEG-fused PNAs is greatly reduced as measured by counts of sensory and/or motor axons, and maintenance of axonal diameters and neuromuscular synapses. After PEG-fusion repair, cut- or crush-severed or ablated PNAs or crush-severed STAs rapidly (within days to weeks), more completely, and permanently restore PNA- or STA-mediated behaviors compared to non-treated or conventionally-treated animals. PEG-fusion success is enhanced or decreased by applying anti-oxidants or oxidants, trimming cut ends or stretching axons, exposure to Ca2+-free or - containing solutions, respectively. PEG-fusion technology employs surgical techniques and chemicals already used by clinicians and has the potential to produce a paradigm-shift in the treatment of traumatic injuries to PNAs and STAs.