Valproic Acid Labeled Chitosan Nanoparticles Promote the Proliferation and Differentiation of Neural Stem Cells After Spinal Cord Injury

Neurotox Res. 2021 Apr;39(2):456-466. doi: 10.1007/s12640-020-00304-y. Epub 2020 Nov 28.

Abstract

Chitosan nanoparticles and valproic acid are demonstrated as the protective agents in the treatment of spinal cord injury (SCI). However, the effects of valproic acid-labeled chitosan nanoparticles (VA-CN) on endogenous spinal cord neural stem cells (NSCs) following SCI and the underlying mechanisms involved remain to be elucidated. In this study, the VA-CN was constructed and the effects of VA-CN on NSCs were assessed in a rat model of SCI. We found VA-CN treatment promoted recovery of the tissue and locomotive function following SCI. Moreover, administration of VA-CN significantly enhanced neural stem cell proliferation and the expression levels of neurotrophic factors following SCI. Furthermore, administration of VA-CN led to a decrease in the number of microglia following SCI. In addition, VA-CN treatment significantly increased the Tuj 1- positive cells in the spinal cord of the SCI rats, suggesting that VA-CN could enhance the differentiation of NSCs following SCI. In conclusion, these results demonstrated that VA-CN could improve the functional and histological recovery through promoting the proliferation and differentiation of NSCs following SCI, which would provide a newly potential therapeutic manner for the treatment of SCI.

Keywords: Differentiation; Neural stem cells; Neurotrophic factors; Proliferation; Spinal cord injury; Valproic acid labeled chitosan nanoparticles.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Chitosan / administration & dosage*
  • Locomotion / drug effects
  • Male
  • Nanoparticles / administration & dosage*
  • Neural Stem Cells / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / physiopathology*
  • Valproic Acid / administration & dosage*

Substances

  • Valproic Acid
  • Chitosan