ArticleOncotarget2017
Metformin ameliorates sepsis-induced brain injury by inhibiting apoptosis, oxidative stress and neuroinflammation via the PI3K/Akt signaling pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Long-Term Cognitive Outcomes After Sepsis: a Translational Systematic Review.Molecular neurobiology · 2019Pooled it
- The "Double-Edged Sword" of Neutrophils in Trauma: From Pathophysiological Mechanisms to Precision Immunomodulation Strategies.International journal of molecular sciences · 2026Review
- Metabolic reprogramming in sepsis-associated encephalopathy: emerging mechanisms, candidate biomarkers, and future therapeutic directions.Frontiers in medicine · 2026Review
- Neuroprotective Roles of Metformin in a Streptozotocin-Induced Dementia Model in Rats.Neurotoxicity research · 2025Article
- Metformin Improves Spatial Memory and Reduces Seizure Severity in a Rat Model of Epilepsy and Alzheimer's Disease comorbidity via PI3K/Akt Signaling Pathway.Molecular neurobiology · 2025Article
- Endothelial TREM-1 mediates sepsis-induced blood‒brain barrier disruption and cognitive impairment via the PI3K/Akt pathway.Journal of neuroinflammation · 2025Article
- Association of metformin administration after septic shock with short-term and long-term survival in septic shock patients with diabetes.Annals of intensive care · 2025Article
- PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy.Open medicine (Warsaw, Poland) · 2025Review
- Metformin Protects Against Acute Kidney Injury Induced by Lipopolysaccharide via Up-Regulating the MCPIP1/SIRT1 Pathway.Biochemical genetics · 2024Article
- Mitochondrial dysfunction in sepsis: mechanisms and therapeutic perspectives.Critical care (London, England) · 2024Review
- From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction.International journal of molecular sciences · 2024Review
- A Mechanism of Action of Metformin in the Brain: Prevention of Methylglyoxal-Induced Glutamatergic Impairment in Acute Hippocampal Slices.Molecular neurobiology · 2024Article
- Beneficial effects of metformin treatment on memory impairment.Molecular biology reports · 2024Review
- Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.Burns & trauma · 2024Review
- Effects of metformin on parasitological, pathological changes in the brain and liver and immunological aspects during visceral toxocariasis in mice.Parasitology research · 2023Article
- Anti‑inflammatory effect of metformin against an experimental model of LPS‑induced cytokine storm.Experimental and therapeutic medicine · 2023Article
- Underdiagnosed CKD in Geriatric Trauma Patients and Potent Prevention of Renal Impairment from Polypharmacy Risks through Individual Pharmacotherapy Management (IPM-III).Journal of clinical medicine · 2023Article
- NF-κB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes mellitus: A narrative review and new perspective.Journal of cellular and molecular medicine · 2023Review
- Paediatric sepsis-associated encephalopathy (SAE): a comprehensive review.Molecular medicine (Cambridge, Mass.) · 2023Review
- Effect of metformin on sepsis-associated acute lung injury and gut microbiota in aged rats with sepsis.Frontiers in cellular and infection microbiology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis-induced brain injuries increase mortality, morbidity, cognitive impairment and lack of effective therapeutic treatment. Previous studies have suggested that metformin provides neuroprotective effects against ischemia, brain trauma and other brain damage, but whether metformin protects a septic brain remains unknown. Thus, the aim of this study is to investigate the possible effects and the mechanism of metformin against septic brain damage using the cecal ligation and puncture (CLP) model. Mice were randomly divided into five groups: the Sham group, CLP group, CLP+ Met group, CLP+ vehicle group and CLP+ Met+ LY group. The survival percentage and brain water content were examined, and the Morris water maze was conducted to determine the protective effect of metformin. Neuronal apoptosis in the cerebral cortex, striatum and hippocampus was examined using TUNEL assay and immunohistochemistry, and western blot was applied to measure the expression of p-Akt. The results indicate that metformin can increase survival percentage, decrease brain edema, preserve the blood-brain barrier (BBB) and improve cognitive function. Metformin also reduced the neuronal apoptosis induced by sepsis and increased the phosphorylation of Akt. However, the protective effect of metformin can be reversed by LY294002, a PI3K inhibitor. In summary, our results demonstrate that metformin can exert a neuroprotective effect by activating the PI3K/Akt signaling pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.