ArticlePharmacological reports : PR2022
The effect of chronic exposure to metformin in a new type-2 diabetic NONcNZO10/LtJ mouse model of stroke.
Article in Pharmacological reports : PR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 4 citations in OpenAlex.
- Acute Low Dose Naltrexone Increases β-Endorphin and Promotes Neuronal Recovery Following Hypoxia-Ischemic Stroke in Type-2 Diabetic Mice.Neurochemical research · 2023Article
- Metformin treatment and acute ischemic stroke outcomes in patients with type 2 diabetes: a retrospective cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
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4 authors at 2 institutions in 1 country.
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Abstract
backgroundDiabetes is an independent risk factor of stroke and previous studies have confirmed that diabetic patients and animals experience poorer clinical outcomes following stroke. In this study, we aim to determine the effect of chronic exposure of the first-line antidiabetic agent, metformin, to restore euglycemia and to impact brain cell death following stroke in a new type-2 diabetes, NONcNZO10/LtJ (RCS-10) mouse model of stroke.
methodsMale RCS-10 mice received a moderate (11%) fat diet post-weaning, at 4 weeks of age, and became diabetic by 12-14 weeks, thus resembling human maturity-onset diabetes. The mice received either metformin or vehicle for 4 weeks before undergoing a hypoxic/ischemic (HI) insult. Blood samples were collected pre-, post-treatment, and post HI for glucose and lipid measurements, and brains were analyzed for infarct size, glial activation, neuronal cell death, and metformin-mediated adenosine monophosphate-activated protein kinase (AMPK) signaling at 48 h post HI.
resultsPretreatment with metformin maintained euglycemia for 4 weeks but did not change body weight or lipid profile. Metformin treatment significantly enhanced the microglial Bfl-1 mRNA expression and showed a non-significant increase in GFAP mRNA, however, GFAP protein levels were reduced. Metformin treatment slightly increased neuronal NeuN and MAP-2 protein levels and significantly reduced overall mortality post HI but did not elicit any significant change in infarct size.
conclusionThe study suggests that the prolonged effect of metformin-induced euglycemia promoted the microglial activation, reduced neuronal cell death, and improved the overall survival following stroke, without any change in infarct size.
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