Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury
| Autor: | Cindi M. Morshead, Parvati Dadwal, Fredric E. Wondisford, Laleh Sinai, Freda D. Miller, Neemat Mahmud, Ashkan Azimi, Michael P. Fatt |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Neurogenesis
Endogeny Biology Biochemistry Mice Neural Stem Cells Cell Movement Precursor cell Report Genetics Neonatal brain medicine otorhinolaryngologic diseases Animals Progenitor cell lcsh:QH301-705.5 Cells Cultured lcsh:R5-920 Brain Cell Biology Functional recovery Neural stem cell Metformin Mice Inbred C57BL stomatognathic diseases Neuroprotective Agents lcsh:Biology (General) Brain Injuries lcsh:Medicine (General) Neuroscience Developmental Biology medicine.drug |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 5, Iss 2, Pp 166-173 (2015) |
| ISSN: | 2213-6711 |
| Popis: | Summary 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. Highlights • Metformin activates endogenous NPCs in the neonatal brain • Metformin increases the absolute number of NPCs after neonatal brain injury • Sensory-motor functional recovery occurs following metformin treatment post-injury Inducing self-repair of the injured brain through activation of endogenous neural precursors is a promising strategy for treating childhood brain injury. Morshead and colleagues use lineage tracking and behavioral assays to reveal that metformin treatment following a neonatal brain injury leads to neural precursor cell expansion, migration, and differentiation in the brain parenchyma and sensory-motor functional recovery. |
| Databáze: | OpenAIRE |
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