Lithium accelerates functional motor recovery by improving remyelination of regenerating axons following ventral root avulsion and reimplantation

Neuroscience. 2016 Aug 4:329:213-25. doi: 10.1016/j.neuroscience.2016.05.010. Epub 2016 May 13.

Abstract

Brachial plexus injury (BPI) often involves the complete or partial avulsion of one or more of the cervical nerve roots, which leads to permanent paralysis of the innervated muscles. Reimplantation surgery has been attempted as a clinical treatment for brachial plexus root avulsion but has failed to achieve complete functional recovery. Lithium is a mood stabilizer drug that is used to treat bipolar disorder; however, its effects on spinal cord or peripheral nerve injuries have also been reported. The purpose of this study was to investigate whether lithium can improve functional motor recovery after ventral root avulsion and reimplantation in a rat model of BPI. The results showed that systemic treatment with a clinical dose of lithium promoted motor neuron outgrowth and increased the efficiency of motor unit regeneration through enhanced remyelination. An analysis of myelin-associated genes showed that the effects of lithium started during the early phase of remyelination and persisted through the late stage of the process. Efficient remyelination of the regenerated axons in the lithium-treated rats led to an earlier functional recovery. Therefore, we demonstrated that lithium might be a potential clinical treatment for BPI in combination with reimplantation surgery.

Keywords: avulsion; lithium; motor function; reimplantation; remyelination; ventral root.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects*
  • Axons / pathology
  • Axons / physiology
  • Brachial Plexus / drug effects
  • Brachial Plexus / injuries
  • Brachial Plexus / physiopathology
  • Brachial Plexus / surgery
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Female
  • Lithium Compounds / pharmacology*
  • Motor Neurons / drug effects
  • Motor Neurons / pathology
  • Motor Neurons / physiology
  • Myelin Sheath / drug effects*
  • Myelin Sheath / pathology
  • Myelin Sheath / physiology
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Replantation
  • Spinal Nerve Roots / drug effects*
  • Spinal Nerve Roots / injuries
  • Spinal Nerve Roots / physiopathology
  • Spinal Nerve Roots / surgery

Substances

  • Lithium Compounds
  • Neuroprotective Agents