Axotomy or compression is required for axonal sprouting following end-to-side neurorrhaphy

Axotomy or compression is required for axonal sprouting following end-to-side neurorrhaphy
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DOI:
10.1016/j.expneurol.2008.02.031
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发表时间:
2008-06-01
影响因子:
5.3
通讯作者:
Myckatyn, Terence M.
Myckatyn, Terence M.
中科院分区:
医学2区
文献类型:
--
作者:
Hayashi, Ayato;Pannucci, Christopher;Myckatyn, Terence M.

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端到侧(ETS)神经修复仍然是周围神经外科医生科学家密切关注的领域。在这项技术中,代表“受体”的受伤神经的横切端被缝合到未受伤的“供体”神经的一侧。一些研究表明,受体肢体是用来自供体神经的再生侧支轴突芽重新填充的,这些轴突芽继续形成功能性突触。重要的,未解决的问题包括供体神经是否需要受伤以促进再生,以及单个供体神经元是否能够投射额外的轴突,这些轴突能够差异地支配不同的靶点。我们连续成像活的转基因小鼠(n=66)表达光谱变体的GFP在各种神经元亚群后,经历了先前描述的无创伤,压缩,或神经外膜切开术形式的ETS修复(n=22每组)。为了评估这些再生轴突的来源和靶神经支配,通过共聚焦显微镜和Western印迹分析进一步补充了神经形态测定和逆行标记。无论是压缩或神经外膜不可避免的轴突切断术,以促进轴突再生到受体肢体。逐渐损伤的模型与受体神经再支配的改善有关(神经外膜切开术:184 +/- 57.6个有髓轴突;压迫:78.9 +/- 13.8;无创伤:0),增加雪旺细胞增殖(神经外膜切开术:增加72.2%;压迫:增加39%)和cAMP反应元件结合蛋白表达,代价是修复远端供体轴突计数的净缺陷。这些差异表现为150天,在这一点上修剪的定量证据。我们的结论是,ETS修复依赖于损伤的供体神经。(C)2008年爱思唯尔公司All rights reserved.
End-to-side (ETS) nerve repair remains an area of intense scrutiny for peripheral nerve surgeon-scientists. In this technique, the transected end of an injured nerve, representing the "recipient" is sutured to the side of an uninjured "donor" nerve. Some works suggest that the recipient limb is repopulated with regenerating collateral axonal sprouts from the donor nerve that go on to form functional synapses. Significant, unresolved questions include whether the donor nerve needs to be injured to facilitate regeneration, and whether a single donor neuron is capable of projecting additional axons capable of differentially innervating disparate targets. We serially imaged living transgenic mice (n=66) expressing spectral variants of GFP in various neuronal subsets after undergoing previously described atraumatic, compressive, or epineurotomy forms of ETS repair (n=22 per group). To evaluate the source, and target innervation of these regenerating axons, nerve morphometry and retrograde labeling were further supplemented by confocal microscopy as well as Western blot analysis. Either compression or epineurotomy with inevitable axotomy were required to facilitate axonal regeneration into the recipient limb. Progressively more injurious models were associated with improved recipient nerve reinnervation (epineurotomy: 184 +/- 57.6 myelinated axons; compression: 78.9 +/- 13.8; atraumatic: 0), increased Schwann cell proliferation (epineurotomy: 72.2% increase; compression: 39% increase) and cAMP response-element binding protein expression at the expense of a net deficit in donor axon counts distal to the repair. These differences were manifest by 150 days, at which point quantitative evidence for pruning was obtained. We conclude that ETS repair relies upon injury to the donor nerve. (C) 2008 Elsevier Inc. All rights reserved.