Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons

PLoS One. 2013;8(1):e54519. doi: 10.1371/journal.pone.0054519. Epub 2013 Jan 18.

Abstract

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might contribute to the restorative effects of these implants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axotomy
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Male
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factors / metabolism
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / transplantation*
  • Neurons* / cytology
  • Neurons* / metabolism
  • Rats
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Vascular Endothelial Growth Factor A
  • Nerve Growth Factor

Grants and funding

The study was funded by grants in Spain BFU2009-07121 and BFU2012-33975 from MEC-FEDER and CVI-6053 from Junta de Andalucía-FEDER. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.