Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier St., Suite D, New Orleans, LA, 70112, USA.
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, 45221, USA.
Mol Neurobiol. 2018 Feb;55(2):1236-1243. doi: 10.1007/s12035-017-0390-0. Epub 2017 Jan 21.
Damage to cutaneous nerves inhibits wound healing in patients. Results from animals on the nerve contributions to healing are various and sometimes contradictory. Here, we aim to clearly define the collective role of central, caudal, and rostral nerves in ear wound healing of mice, rats, and rabbits. These wounds heal with minimal contraction like wounds in humans. We resected central, caudal, and rostral nerves at the base of ear pinnae by microsurgery and created excisional full-thickness skin wounds in the pinnae neurologically downstream from the resections. Denervation in mice resulted in no closure for 14 days post-wounding (dpw) and led to only 17.2% closure at 21 dpw when the excisional wounds of non-denervated ear pinnae were completely closed. Compared to excisional wounds that were not denervated in sham surgery, wounds with denervation showed an increase of excisional wound areas for 5.0% by 7 dpw and a 43.7% reduction of wound closure at 12 dpw for rats. In rabbits, denervation attenuated wound closure for 14.2, 34.4, and 28.3% at 7, 14, and 18 dpw, respectively. Our histological analysis showed marked denervation impairment in pivotal healing processes, re-epithelialization and granulation tissue growth, suggesting denervation impairment in the regeneration of blood capillaries and/or connective tissue in wounds. These results reveal the critical contributions made by central, caudal, and rostral nerves in ear pinnae to minimal-contraction skin wound healing. Our study also provides small animal models of minimal-contraction wound healing of denervated ear skins that recapitulate human wound healing involving surgical or traumatic nerve damages.
皮肤神经损伤会抑制患者的伤口愈合。动物实验结果表明，神经对伤口愈合的贡献多种多样，有时甚至相互矛盾。在这里，我们旨在明确定义中枢神经、尾侧神经和吻侧神经在小鼠、大鼠和兔子的耳部伤口愈合中的集体作用。这些伤口的愈合方式与人类的伤口相似，几乎没有收缩。我们通过微创手术切除耳郭基部的中枢神经、尾侧神经和吻侧神经，并在神经切除下游的耳郭皮瓣上创建全层皮肤切除性创面。在小鼠中，神经切断术导致 14 天（dpw）后无法闭合，当非神经切断的耳郭切除性创面完全闭合时，21 dpw 时仅闭合 17.2%。与假手术中未神经切断的切除性创面相比，神经切断的创面在 7 dpw 时增加了 5.0%的切除性创面面积，在 12 dpw 时减少了 43.7%的创面闭合。在兔子中，神经切断术分别导致 14.2%、34.4%和 28.3%的伤口闭合延迟，在 7、14 和 18 dpw 时。我们的组织学分析显示，关键的愈合过程，如再上皮化和肉芽组织生长，存在明显的神经切断损伤，这表明神经切断术损害了伤口中毛细血管和/或结缔组织的再生。这些结果揭示了耳郭的中枢神经、尾侧神经和吻侧神经在微小收缩性皮肤伤口愈合中的关键作用。我们的研究还提供了神经切断的耳皮微小收缩性创面愈合的小型动物模型，模拟了涉及手术或创伤性神经损伤的人类创面愈合。
