ArticleBrain, behavior, & immunity - health2020
Subacute metformin treatment reduces inflammation and improves functional outcome following neonatal hypoxia ischemia.
Article in Brain, behavior, & immunity - health, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Maternal metformin protects developing auditory brainstem function after neonatal hypoxia-ischemia in a neonatal rat model.Clinical and experimental pediatrics · 2026Article
- Antenatal strategies for prevention of neonatal hypoxic-ischemic encephalopathy: potential role of metformin.Clinical and experimental pediatrics · 2026Article
- Early ultrasound-based assessment of preterm white matter injury: association with MRI and neurological outcomes.Pediatric radiology · 2026Article
- Safety and feasibility trial protocol of metformin in infants after perinatal brain injury.BMJ paediatrics open · 2025Article
- Review
- Role of Microglial Modulation in Therapies for Perinatal Brain Injuries Leading to Neurodevelopmental Disorders.Advances in neurobiology · 2024Review
- Metformin attenuates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Metformin Improves Functional Outcomes, Activates Neural Precursor Cells, and Modulates Microglia in a Sex-Dependent Manner After Spinal Cord Injury.Stem cells translational medicine · 2023Article
- Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke.Journal of neuroinflammation · 2022Article
- Review
- Metformin effects on brain development following cranial irradiation in a mouse model.Neuro-oncology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-ischemia (HI) injury is a leading cause of neonatal death and long-term disability, and existing treatment options for HI offer only modest benefit. Early intervention with the drug metformin has been shown to promote functional improvement in numerous rodent models of injury and has pleiotropic cellular effects in the brain. We have previously shown that 1 week of metformin treatment initiated 24 h after HI in neonatal mice resulted in improved motor and cognitive performance, activation of endogenous neural precursor cells (NPCs), and increased oligodendrogenesis. While promising, a limitation to this work is that immediate pharmacological intervention is not always possible in the clinic. Herein, we investigated whether delaying metformin treatment to begin in the subacute phase post-HI would still effectively promote recovery. Male and female C57/BL6 mice received HI injury postnatally, and metformin treatment began 7 days post-HI for up to 4 weeks. Motor and cognitive performance was assessed across time using behavioural tests (cylinder, foot fault, puzzle box). We found that metformin improved motor and cognitive behaviour, decreased inflammation, and increased oligodendrocytes in the motor cortex. Our present findings demonstrate that a clinically relevant subacute metformin treatment paradigm affords the potential to treat neonatal HI, and that improved outcomes occur through modulation of the inflammatory response and oligodendrogenesis.
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