Metformin Applications in Cerebral Ischemia

Metformin, long established as a first‐line treatment for type 2 diabetes, has attracted considerable interest for its neuroprotective properties in cerebral ischaemia. Preclinical models demonstrate that metformin modulates cellular metabolism, primarily via activation of AMP-activated protein kinase (AMPK), leading to reduced oxidative stress, attenuation of inflammatory signalling and preservation of blood–brain barrier integrity. In parallel, clinical cohort studies suggest that pre‐stroke metformin use is associated with decreased infarct volumes, improved neurological function and lower mortality. Mechanistic investigations highlight the drug’s ability to up-regulate brain-derived neurotrophic factor (BDNF) through the AMPK/CREB pathway, promote angiogenesis and limit neuronal apoptosis. Together, these findings support repurposing metformin as an adjunctive therapy to enhance stroke outcomes and address the global burden of ischaemic brain injury.

Research from Nature Portfolio

Chronic metformin pre-conditioning in a non-diabetic mouse model of chronic kidney disease was shown to rescue AMPK activity in ischaemic brain tissue, reduce infarct volume and improve sensorimotor performance. Treatment enhanced neuronal survival, reduced apoptosis and suppressed microglial M1 polarisation by inhibiting canonical NF-κB signalling, thereby demonstrating that metformin can prevent stroke damage through restoration of energy homeostasis and attenuation of post-ischaemic inflammation.

Metformin Applications in Cerebral Ischemia publication trend

The graph below shows the total number of articles in metformin applications in cerebral ischemia across all publications each year (not limited to Nature Index journals).

Technical terms

Cerebral ischaemia: Reduction of blood flow to brain tissue causing oxygen and glucose deprivation.

Ischaemia/reperfusion injury: Cellular damage incurred when blood supply is restored after an ischaemic episode, driven by oxidative stress and inflammatory cascades.

AMP‐activated protein kinase (AMPK): A master regulator of cellular energy balance activated under metabolic stress.

Blood–brain barrier (BBB): A selective endothelial interface that controls passage of substances from the circulation into the central nervous system.

Brain-derived neurotrophic factor (BDNF): A neurotrophin essential for neuronal survival, differentiation and synaptic plasticity.

References

1. Effectiveness of metformin pretreatment for stroke severity: A propensity score matching study. CNS Neuroscience & Therapeutics (2024).
2. Effects of Prior Metformin Use on Stroke Outcomes in Diabetes Patients with Acute Ischemic Stroke Receiving Endovascular Treatment. Biomedicines (2024).
3. Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion. Journal of Neuroinflammation (2014).
4. Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury via Regulation of the AMPK/CREB/BDNF Pathway. Frontiers in Pharmacology (2022).
5. Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease. Scientific Reports (2021).