Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury

Stem Cell Reports. 2015 Aug 11;5(2):166-73. doi: 10.1016/j.stemcr.2015.06.011. Epub 2015 Jul 30.

Abstract

The development of cell replacement strategies to repair the injured brain has gained considerable attention, with a particular interest in mobilizing endogenous neural stem and progenitor cells (known as neural precursor cells [NPCs]) to promote brain repair. Recent work demonstrated metformin, a drug used to manage type II diabetes, promotes neurogenesis. We sought to determine its role in neural repair following brain injury. We find that metformin administration activates endogenous NPCs, expanding the size of the NPC pool and promoting NPC migration and differentiation in the injured neonatal brain in a hypoxia-ischemia (H/I) injury model. Importantly, metformin treatment following H/I restores sensory-motor function. Lineage tracking reveals that metformin treatment following H/I causes an increase in the absolute number of subependyma-derived NPCs relative to untreated H/I controls in areas associated with sensory-motor function. Hence, activation of endogenous NPCs is a promising target for therapeutic intervention in childhood brain injury models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / growth & development
  • Brain Injuries / drug therapy*
  • Cell Movement
  • Cells, Cultured
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neurogenesis*
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use

Substances

  • Neuroprotective Agents
  • Metformin