中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1852-1856.doi: 10.4103/1673-5374.363180

• 原著:周围神经损伤修复保护与再生 • 上一篇    

神经导管中的周围神经再生诱发脊髓中生长相关蛋白43的差异表达

  

  • 出版日期:2023-08-15 发布日期:2023-02-24

Peripheral nerve regeneration through nerve conduits evokes differential expression of growth-associated protein-43 in the spinal cord

Jesús Chato-Astrain1, #, Olga Roda2, #, David Sánchez-Porras1, Esther Miralles3, Miguel Alaminos1, Fernando Campos1, Óscar Darío García-García1, *, Víctor Carriel1, *   

  1. 1Department of Histology (Tissue Engineering Group), University of Granada, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; 2Department of Human Anatomy and Embryology, University of Granada, Granada, Spain; 3Unit of Clinical Neurophysiology, University Hospital San Cecilio, Granada, Spain
  • Online:2023-08-15 Published:2023-02-24
  • Contact: Óscar Darío García-García, MSc, PhD, ogarcia@ugr.es; Víctor Carriel, MSc, PhD, MBiol PhD, vcarriel@ugr.es.
  • Supported by:
    The study was financed by the Spanish “Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad (Instituto de Salud Carlos III)”, grant Nos: FIS PI17-0393, FIS PI20-0318, co-financed by the “Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union”; grant No. P18-RT-5059 by “Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020), Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, España”; and grant No. A-CTS-498-UGR18 by “Programa Operativo FEDER Andalucía 2014-2020, Universidad de Granada, Junta de Andalucía, España”, co-funded by ERDF-FEDER, the European Union (all to VC).

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摘要：

生长相关蛋白43通过细胞骨架重塑在神经突起生长中起关键作用。作者以往研究已经证明，周围神经的结构损伤诱导生长相关蛋白43上调，以促进生长锥的形成。然而，抑制性微环境导致的中枢神经系统轴突生长受阻应该与生长相关蛋白43表达的低水平相关。为评估外周神经损伤引起的中枢神经系统改变，实验利用NeuraGen胶原神经导管修复大鼠1cm长坐骨神经缺损，并检测生长相关蛋白43标志物在周围和中枢神经系统的表达。首先，组织学分析证实了从修复后10d起通过导管的神经再生过程。生长相关蛋白43表达存在从局部到整个再生组织中的丰富和一致性，证实了活跃神经再生过程的存在。其次，脊髓的组织学常规染色方法评估发现，在组织和细胞结构方面无明显的变化。然而，令人惊讶的是，生长相关蛋白43在脊髓水平的表达出现了重要的差异和局部变化，特别是在修复后20天以后。生长相关蛋白43免疫反应首先定位于薄束，然后均匀分布于左后索；而健康对照在这些部位不表达生长相关蛋白43。实验结果揭示了生长相关蛋白43不仅在再生的神经组织中存在差异表达，而且在周围神经切断后的脊髓中也存在差异表达。这一发现使应用生长相关蛋白43评估周围神经损伤后中枢神经系统变化成为可能性。

https://orcid.org/0000-0002-4710-0733 (Óscar Darío García-García); https://orcid.org/0000-0002-8114-5644 (Víctor Carriel)

Abstract: Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling. We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation. Conversely, the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression. However, central alterations due to peripheral nerve damage have never been assessed using the growth-associated protein 43 marker. In this study, we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems. First, histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards. The growth-associated protein 43 expression profile varied across regions and follow-up times, from a localized expression to an abundant and consistent expression throughout the regeneration tissue, confirming the presence of an active nerve regeneration process. Second, spinal cord changes were also histologically assessed, and no apparent changes in the structural and cellular organization were observed using routine staining methods. Surprisingly, remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level, in particular at 20 days post-repair and beyond. Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord. These findings differed from the growth-associated protein 43 pattern observed in the healthy control, which did not express growth-associated protein 43 at these levels. Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection. These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.

Key words: growth-associated protein 43 (GAP-43), immunohistochemistry, nerve guide, nerve tissue regeneration, peripheral nerve repair, spinal cord, tissue engineering