SummaryThe 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.

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Parkinson's disease (PD) is a common neurodegenerative disorder that results from the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Studies show that mitochondrial dysfunction/oxidative stress is a major contributor to this disease. Currently there is no treatment to halt the progression of PD. Recently we have shown that water‐soluble coenzyme Q10 (WS‐CoQ10, NRC technology licensed to Zymes LLC) prevents the loss of dopaminergic neurons in the SNpc and ameliorates the symptoms of paraquat (PQ)‐inducted PD in the rat model. We have observed that there is activation of astroglia in the brains of WS‐CoQ10 treated animals. Whether this activation plays a role in protecting SNpc neurons is unknown. It is possible that activated astroglia cells produce neurotrophic factors that may protect neurons under oxidative stress. We analyzed brain tissue samples from PQ treated PD rats fed with either placebo or WS‐CoQ10 for DA neurons, activation of astroglia and levels of various neurotrophic growth factors. We observed significant protection of DA neurons in the SNpc, activated astroglia and increased levels of BDNF and GDNF in WS‐CoQ10 fed rats. These results indicate that WS‐CoQ10 treatment could activate astroglia that produce high levels of BDNF and GDNF and could provide protection to the DA neurons against PQ toxicity and may be used to halt PD progression.Funded by CIHR.