Nerve regeneration in rat peripheral nerve allografts: Evaluation of cold-inducible RNA-binding protein in nerve storage and regeneration

J Comp Neurol. 2019 Dec 1;527(17):2885-2895. doi: 10.1002/cne.24716. Epub 2019 Jun 2.

Abstract

The prevalence of peripheral nerve injury has attracted increased attention. Allografting has been proposed as a potential treatment strategy for peripheral nerve injury. Moreover, cryopreservation may provide almost unlimited graft material. We investigated whether cold-inducible RNA-binding protein (CIRP) could protect peripheral nerves during cryopreservation to promote regeneration postoperation. First, CIRP was highly expressed after pretreatment at 32°C. After 4 weeks of cryopreservation, the increased live cells, low Bax/Bcl-2 ratio and high nerve growth factor and glial cell-derived neurotrophic factor levels in the 32°C group demonstrated high nerve graft viability. At 4 weeks postoperation, 32°C-Allo group demonstrated low plasma levels of interleukin-6 and interferon-gamma and a diminished cellular immune response. At 20 weeks postoperation, nerve regeneration in the 32°C-Allo group was similar to that in the fresh isograft group and superior to that in the 4°C-Allo and 15°C-Allo groups. Moreover, the compound muscle action potential and the motor nerve conduction velocity of the 32°C-Allo group were equal to those of the fresh isograft group. In conclusion, CIRP induction increased Schwann cell biological activity, inhibited cell apoptosis, reduced immune rejection, and promoted recipient nerve regeneration. Thus, CIRP could exert protective effects during nerve storage and stimulate regeneration in peripheral nerve reconstruction.

Keywords: CIRP; RRID:AB_10701879; RRID:AB_10863015; RRID:AB_2073233; RRID:AB_2111379; RRID:AB_838305; RRID:AB_867795; RRID:AB_881254; Schwann cells; allograft; cryopreservation; nerve regeneration; peripheral nerve injury; viability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Axons / drug effects
  • Axons / pathology
  • Axons / physiology
  • Cold Shock Proteins and Peptides / metabolism
  • Cold Shock Proteins and Peptides / pharmacology*
  • Cryopreservation / methods
  • Cryoprotective Agents / pharmacology*
  • Graft Rejection / prevention & control
  • Interleukin-6 / blood
  • Male
  • Muscle, Skeletal / physiopathology
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neuroprotective Agents / pharmacology*
  • Peripheral Nerve Injuries / drug therapy
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / physiopathology
  • Peripheral Nerve Injuries / surgery*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / pharmacology*
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiopathology
  • Sciatic Nerve / transplantation*
  • Transplantation, Homologous

Substances

  • Cirbp protein, rat
  • Cold Shock Proteins and Peptides
  • Cryoprotective Agents
  • Il6 protein, rat
  • Interleukin-6
  • Neuroprotective Agents
  • RNA, Messenger
  • RNA-Binding Proteins