MicroRNA-338 and microRNA-21 co-transfection for the treatment of rat sciatic nerve injury

Neurol Sci. 2016 Jun;37(6):883-90. doi: 10.1007/s10072-016-2500-6. Epub 2016 Feb 24.

Abstract

The objective of this study is to find if co-transfecting microRNA-338 and microRNA-21 into the neurons in the spinal cord can promote functional recovery after peripheral nerve injury in rats. Animals were divided into three groups: 20 animals in the GFP control vector group (group A), 20 animals in the GFP experimental vector group (group B) and ten animals in the normal control group. Right sciatic nerves of animals in groups A and B were transected and were bridged with collagen nerve conduits with 10 mm distance between the stumps. 3 µl GFP control vector or 3 µl lentiviral vectors encoding the sequence of microRNA-338 and microRNA-21 were injected in the conduit. 8 weeks after the surgery, the treatment effect was evaluated by functional analysis, electrophysiological analysis, immunohistochemical analysis as well as transmitting electronic microscope observations in all the rats. Animals treated with microRNA-338 and microRNA-21 showed significantly better recovery than GFP control group animals by means of functional analysis (Sciatic nerve index -47.7 ± 2.5 vs -59.4 ± 3.7), electrophysiological analysis (Conduction velocity 20.5 ± 2.8 vs 10.5 ± 1.4 m/s), ratio of wet weight of the gastrocnemius muscles (0.83 ± 0.03 vs 0.55 ± 0.06), axon diameter (5.0 ± 1.8 µm vs 4.0 ± 2.2), myelin sheath thickness (1.4 ± 0.43 vs 0.80 ± 0.31 µm) and G-ratio (0.80 ± 0.06 vs 0.75 ± 0.04). Lentiviral vectors encoding microRNA 338 and 21 might be explored in the future as potential therapeutic intervention to promote nerve regeneration.

Keywords: MicroRNA-338, microRNA-21; Nerve conduit; Nerve injury; Peripheral; Sciatic nerve.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Axons / pathology
  • Axons / ultrastructure
  • Disease Models, Animal
  • Evoked Potentials / physiology
  • Follow-Up Studies
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / therapeutic use*
  • Microscopy, Electron, Transmission
  • Muscle, Skeletal / pathology
  • Neurofilament Proteins / metabolism
  • Organ Size / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / genetics
  • Sciatic Nerve / pathology
  • Sciatic Nerve / ultrastructure
  • Sciatic Neuropathy / genetics
  • Sciatic Neuropathy / pathology
  • Sciatic Neuropathy / therapy*
  • Severity of Illness Index
  • Transfection*

Substances

  • MIRN338 microRNA, rat
  • MicroRNAs
  • Neurofilament Proteins
  • mirn21 microRNA, rat
  • neurofilament protein H
  • Acetylcholinesterase