Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment

Int J Pharm. 2017 Mar 15;519(1-2):323-331. doi: 10.1016/j.ijpharm.2017.01.036. Epub 2017 Jan 20.

Abstract

Recruiting neural stem cell (NSC) at the lesion site is essential for central nervous system repair. This process could be triggered by the local delivery of the chemokine SDF-1. We compared two PLGA formulations for local brain SDF-1 delivery: SDF-1 loaded microspheres (MS) and SDF-1 loaded nanoparticles (NP). Both formulations were able to encapsulate more than 80% of SDF-1 but presented different release profiles, with 100% of SDF-1 released after 6days for the MS and with 25% of SDF-1 released after 2 weeks for NP. SDF-1 bioactivity was demonstrated by a chemotactic assay. When injected in mouse brain after traumatic brain injury, only SDF-1 nanoparticles induced NSC migration to the damage area. More neuroblasts (DCX+ cells) could be visualized around the lesions treated with NP SDF-1 compared to the other conditions. Rostral migratory stream destabilization with massive migration of DCX+ cell toward the perilesional area was observed 2 weeks after NP SDF-1 injection. Local injection of SDF-1-loaded nanoparticles induces recruitment of NSC and could be promising for brain injury lesion.

Keywords: Brain injury; Nanoparticles; Neural stem cells; SDF-1.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain Injuries, Traumatic / drug therapy*
  • Cell Movement / drug effects
  • Central Nervous System Stimulants / administration & dosage*
  • Chemistry, Pharmaceutical / methods
  • Chemokine CXCL12 / administration & dosage*
  • Doublecortin Protein
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Microspheres
  • Nanoparticles / administration & dosage*
  • Neural Stem Cells / drug effects*

Substances

  • Central Nervous System Stimulants
  • Chemokine CXCL12
  • Dcx protein, mouse
  • Doublecortin Protein