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Transient Middle Cerebral Artery Occlusion Model of Stroke
Published on: August 11, 2023
Effects of metformin in experimental stroke
Jun Li1, Sharon E Benashski, Venugopal Reddy Venna
1Department of Neurology, Farmington, CT 06030, USA.
Stroke
|September 18, 2010
Summary
Acute metformin worsened stroke outcomes by activating AMPK, while chronic metformin pre-treatment was neuroprotective. Timing and duration of AMPK activation are crucial for stroke treatment.
Area of Science:
- Neuroscience
- Metabolic Signaling
- Cerebrovascular Disease
Background:
- Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a key energy sensor.
- Stroke-induced AMPK activation is detrimental, as inhibiting or deleting AMPK is neuroprotective.
Purpose of the Study:
- To investigate the impact of acute and chronic metformin administration on infarct volume and AMPK activation in experimental stroke.
- To explore the role of AMPK and neuronal nitric oxide synthase in metformin's effects on stroke.
Main Methods:
- Mice underwent middle cerebral artery occlusion after acute or chronic metformin treatment.
- Infarct volume, AMPK activation, lactate levels, and behavior were assessed.
- AMPK and neuronal nitric oxide synthase knockout mice were used to examine specific roles.
Main Results:
- Acute metformin worsened stroke damage and increased AMPK activation.
- Chronic metformin pre-treatment demonstrated neuroprotective effects, improving metabolic function and reducing AMPK activation.
- Neuroprotective effects of chronic metformin were abolished in neuronal nitric oxide synthase knockout mice.
Conclusions:
- The timing and duration of AMPK activation critically influence its downstream effects in the ischemic brain.
- AMPK represents a potential therapeutic target for stroke treatment and prevention, with metformin's effects being dose- and time-dependent.
