中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (8): 1802-1808.doi: 10.4103/1673-5374.332152

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

缺乏穿孔素利于小鼠损伤股神经的再生?

  

  • 出版日期:2022-08-15 发布日期:2022-01-22
  • 基金资助:
    研究受李嘉诚基金会、波鸿鲁尔大学FoRUM基金F957N-2019以及Heinrich und Alma Vogelsang Stiftung的资助

Mice lacking perforin have improved regeneration of the injured femoral nerve

Igor Jakovčevski1, *, Monika von Düring2, David Lutz2, Maja Vulović3, Mohammad Hamad1, Gebhard Reiss1, Eckart Förster2, Melitta Schachner4, *   

  1. 1Institut für Anatomie und Klinische Morphologie, Universität Witten/Herdecke, Witten, Germany; 2Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany; 3Department of Anatomy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; 4Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA
  • Online:2022-08-15 Published:2022-01-22
  • Contact: Melitta Schachner, PhD, schachner@dls.rutgers.edu; Igor Jakovcevski, MD, Igor.Jakovcevski@uni-wh.de.
  • Supported by:
    This study was supported by the Li Kashing Foundation (to MS), the FoRUM grant F957N-2019 of the Ruhr-University Bochum (to DL), and the Heinrich und Alma Vogelsang Stiftung (to IJ).

摘要:

周围神经系统损伤后,免疫系统所起的作用仍未被完全理解。穿孔素是一种自然杀伤细胞和T淋巴细胞衍生的酶,它能介导细胞毒性,在自身免疫性疾病、感染和中枢神经系统创伤(如脊髓损伤)中起着重要作用。为了剖析穿孔素对周围神经损伤后再生的影响,实验对比了穿孔素缺陷(Pfp-/-)和野生型对照小鼠股神经损伤后的再生情况。单帧运动分析显示,与对照组小鼠相比,Pfp-/-小鼠在伤后48周的运动恢复情况更好。对再生到运动神经分支的运动神经元轴突的逆行追踪显示,与野生型小鼠相比,Pfp-/-小鼠脊髓中的运动神经元投射更准确。在股神经的运动分支中,通过g-ratio测量的再生轴突的髓鞘化在Pfp-/-小鼠中比在野生型小鼠中更广泛。Pfp-/-小鼠受伤后在脊髓运动神经元的细胞体周围显示出比受伤的野生型小鼠更多的胆碱能突触终端。术后10d对淋巴细胞浸润进行的组织学分析发现,Pfp-/-小鼠再生神经中的淋巴细胞数量低于野生型小鼠,表明Pfp-/-小鼠的血-神经屏障封闭。说明由于运动神经元的存活率降低和髓鞘化减少,穿孔素限制了股神经损伤后的运动恢复。

https://orcid.org/0000-0002-3316-0778 (Melitta Schachner); https://orcid.org/0000-0002-6654-8402 (Igor Jakovcevski)

Abstract: The role that the immune system plays after injury of the peripheral nervous system is still not completely understood. Perforin, a natural killer cell- and T-lymphocyte-derived enzyme that mediates cytotoxicity, plays important roles in autoimmune diseases, infections and central nervous system trauma, such as spinal cord injury. To dissect the roles of this single component of the immune response to injury, we tested regeneration after femoral nerve injury in perforin-deficient (Pfp–/–) and wild-type control mice. Single frame motion analysis showed better motor recovery in Pfp–/– mice compared with control mice at 4 and 8 weeks after injury. Retrograde tracing of the motoneuron axons regrown into the motor nerve branch demonstrated more correctly projecting motoneurons in the spinal cord of Pfp–/– mice compared with wild-types. Myelination of regrown axons measured by g-ratio was more extensive in Pfp–/– than in wild-type mice in the motor branch of the femoral nerve. Pfp–/– mice displayed more cholinergic synaptic terminals around cell bodies of spinal motoneurons after injury than the injured wild-types. We histologically analyzed lymphocyte infiltration 10 days after surgery and found that in Pfp–/– mice the number of lymphocytes in the regenerating nerves was lower than in wild-types, suggesting a closed blood-nerve barrier in Pfp–/– mice. We conclude that perforin restricts motor recovery after femoral nerve injury owing to decreased survival of motoneurons and reduced myelination.

Key words: blood-nerve barrier, femoral nerve injury, locomotor recovery, lymphocytes, myelination, NK-cells, perforin, reinnervation