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

Parvati Dadwal, Neemat Mahmud, Laleh Sinai, Ashkan Azimi, Michael Fatt, Fredric E. Wondisford, Freda D. Miller, Cindi M. Morshead

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)166-173
Number of pages8
JournalStem Cell Reports
Volume5
Issue number2
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury'. Together they form a unique fingerprint.

Cite this