Valproic Acid attenuates disease symptoms and increases endogenous myelin repair by recruiting neural stem cells and oligodendrocyte progenitors in experimental autoimmune encephalomyelitis

Neurodegener Dis. 2014;13(1):45-52. doi: 10.1159/000352021. Epub 2013 Aug 16.

Abstract

Background: inefficient remyelination of demyelinated plaques in multiple sclerosis (ms) leads to secondary axon degeneration and progressive disability. therapies that potentiate remyelination would be of immense help for managing MS.

Objective: Here, we report the effects of valproic acid (VPA) on focal experimental autoimmune encephalomyelitis (fEAE).

Methods: fEAE was induced in Wistar rats by immunizing the animals with guinea pig spinal cord homogenate emulsified in complete Freund's adjuvant and with pertussis toxin (PT) injection into the spinal cord at the level of T8 vertebra on day 18 after immunization. VPA 300 mg/kg was applied for 4 days after or 8 days before PT administration. Behavioral evaluation, histological assessment and immunohistofluorescence assays were used to evaluate the outcomes.

Results: VPA administration had no effect on the development of symptoms, but after discontinuing VPA, animals showed faster recovery. Eight days of pretreatment with VPA accelerated the recovery phase of EAE and increased the number of remyelinated axons in the lesion area. VPA pretreatment also increased the recruitment of neural stem cells and oligodendrocyte precursors within the lesion.

Conclusions: Results suggest VPA as a potential therapy for remyelinating the lesions in MS and for faster recovery from disease relapses. The effect of VPA seems to be mediated by endogenous progenitors recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System Agents / therapeutic use*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Fluorescent Antibody Technique
  • Guinea Pigs
  • Nerve Fibers, Myelinated / drug effects*
  • Nerve Fibers, Myelinated / pathology
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / physiology
  • Oligodendroglia / drug effects
  • Oligodendroglia / physiology
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Stem Cells / drug effects*
  • Stem Cells / pathology
  • Valproic Acid / therapeutic use*

Substances

  • Central Nervous System Agents
  • Valproic Acid