ArticleBrain and behavior2021
Neuroprotective effects of metformin on cerebral ischemia-reperfusion injury by regulating PI3K/Akt pathway.
Article in Brain and behavior, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 3 citations in OpenAlex.
- PI3K-Akt signaling network crosstalk in cerebral ischemia/reperfusion injury: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Neuroprotective effects of sinomenine and metformin in diabetic stroke: Role of NLRP3/caspase-1 and mitophagy.Experimental physiology · 2026Article
- Astragaloside IV suppresses neuroinflammation via PI3K/Akt/NF-κB to ameliorate cerebral ischemia-reperfusion injury based on network pharmacology analysis and experimental validation.Frontiers in immunology · 2026Article
- Pharmacological Therapies for Consequences of Perinatal Hypoxic-Ischemic Brain Injury: Where Are We Now?International journal of molecular sciences · 2025Review
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Metformin and the PI3K/AKT signaling pathway: implications for cancer, cardiovascular, and central nervous system diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Environmental Enrichment and Metformin Combination Improves Cognitive Function through BDNF and HPA Axis in Chronically Stressed Rats.Current Alzheimer research · 2025Article
- Lithium reduces cerebral ischemia/reperfusion injury in dexamethasone-treated rats: The role of the PI3K/Akt pathway.Open veterinary journal · 2025Article
- Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy.Molecular neurobiology · 2024Review
- Research progress of propofol in alleviating cerebral ischemia/reperfusion injury.Pharmacological reports : PR · 2024Review
- Identification of Parkinson's disease PACE subtypes and repurposing treatments through integrative analyses of multimodal data.NPJ digital medicine · 2024Article
- Scutellarin alleviates microglia-mediated neuroinflammation and apoptosis after ischemic stroke through the PI3K/AKT/GSK3Journal of cell communication and signaling · 2024Article
- Establishment and Validation of a Model for Fetal Neural Ischemia Using Necrotic Core-Free Human Spinal Cord Organoids.Stem cells translational medicine · 2024Article
- Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury.Biomedicines · 2024Review
- Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy.Journal of clinical medicine · 2023Review
- Metformin mitigates amyloid βMetabolic brain disease · 2023Article
- Dysregulation of mTOR Signaling after Brain Ischemia.International journal of molecular sciences · 2022Review
- Neuroprotective effects of metformin on cerebral ischemia-reperfusion injury by regulating PI3K/Akt pathway.Brain and behavior · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin (Met) is a commonly used drug in the treatment of type 2 diabetes. Currently, it has been found that Met can effectively reduce the incidence of stroke and exert anti-inflammatory effects. However, its role in ischemia-reperfusion (I/R)-induced nerve injury remains unclear. This study aims to investigate the neuroprotective effects of Met in I/R-induced neuron injury as well as the underlying mechanism. A middle cerebral artery occlusion (MCAO) model was established in Sprague Dawley (SD) rats, which were then treated with different doses of Met. Neurological deficits of rats were measured at different times post-surgery. TTC staining was done to observe the volume of cerebral infarction. HE staining was performed to observe pathological changes of brain tissues. Immunohistochemistry was performed to observe the expression of inflammatory factors in the cerebral tissues. qRT-PCR method was used to detect the relative expression of PI3K, Akt mRNA in cells after 24 h of drug action. Western blot method was used to detect the expression of PI3K, p-PI3K, Akt, and p-Akt in hippocampus. What is more, in vitro experiments were performed on BV2 microglia to verify the role of Met against oxygen-glucose deprivation (OGD). As a result, Met dose-dependently attenuated neurological deficits and neuronal apoptosis. Besides, Met administration also significantly reduced BV2 cells apoptosis and inflammatory response. Mechanistically, Met inactivated PI3K/Akt pathway induced by I/R and OGD, while it upregulated PI3K. In conclusion, Met protected rats from cerebral I/R injury via reducing neuronal apoptosis and microglial inflammation through PI3K/Akt pathway.
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