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Updated: May 1, 2026

A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Short-term preoperative dietary restriction is neuroprotective in a rat focal stroke model
Kärt Varendi1, Mikko Airavaara1, Jenni Anttila1
1Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Insights
Short-term preoperative dietary restriction, including fasting and protein restriction, shows promise in reducing stroke severity and improving outcomes in at-risk surgical patients. This neuroprotective strategy may offer a simple approach to mitigate perioperative stroke complications.
Area of Science:
- Neuroscience
- Cardiovascular Surgery
- Metabolic Research
Background:
- Stroke is a significant complication of cardiovascular surgery, leading to substantial mortality and morbidity.
- Current strategies for mitigating perioperative stroke are limited, with few options to reduce incidence or severity preoperatively.
- Preoperative interventions to enhance neuroprotection in at-risk individuals remain largely unexplored.
Purpose of the Study:
- To investigate the neuroprotective potential of short-term preoperative dietary restriction in rat models of focal stroke.
- To assess the impact of fasting and protein-restricted diets on stroke outcomes and molecular markers of damage and protection.
Main Methods:
- Rats were preconditioned with either 3 days of water-only fasting or 6 days of a protein-free diet.
- Transient middle cerebral artery occlusion was induced to model severe and mild focal strokes.
- Infarct volume, functional recovery, and molecular markers of inflammation and damage were evaluated post-reperfusion.
Main Results:
- Three days of preoperative fasting significantly reduced infarct volume in a severe focal stroke model.
- Dietary protein restriction for 6 days improved functional recovery and reduced injury in a mild cortical stroke model.
- Neuroprotection was linked to modulated innate immunity, including altered levels of neutrophil chemoattractant and suppressed pro-inflammatory markers.
Conclusions:
- Short-term dietary restriction, including fasting and protein restriction, can provide significant neuroprotection against focal stroke in preclinical models.
- These findings suggest that preoperative dietary interventions are a viable and translatable strategy to reduce perioperative stroke severity.
- This approach offers a simple method to potentially improve outcomes for patients undergoing high-risk elective vascular surgery.
Abstract:
Stroke is a major complication of cardiovascular surgery, resulting in over 100,000 deaths and over a million postoperative encephalopathies annually in the US and Europe. While mitigating damage from stroke after it occurs has proven elusive, opportunities to reduce the incidence and/or severity of stroke prior to surgery in at-risk individuals remain largely unexplored. We tested the potential of short-term preoperative dietary restriction to provide neuroprotection in rat models of focal stroke. Rats were preconditioned with either three days of water-only fasting or six days of a protein free diet prior to induction of transient middle cerebral artery occlusion using two different methods, resulting in either a severe focal stroke to forebrain and midbrain, or a mild focal stroke localized to cortex only. Infarct volume, functional recovery and molecular markers of damage and protection were assessed up to two weeks after reperfusion. Preoperative fasting for 3 days reduced infarct volume after severe focal stroke. Neuroprotection was associated with modulation of innate immunity, including elevation of circulating neutrophil chemoattractant C-X-C motif ligand 1 prior to ischemia and suppression of striatal pro-inflammatory markers including tumor necrosis factor α, its receptor and downstream effector intercellular adhesion molecule-1 after reperfusion. Similarly, preoperative dietary protein restriction for 6 days reduced ischemic injury and improved functional recovery in a milder cortical infarction model. Our results suggest that short-term dietary restriction regimens may provide simple and translatable approaches to reduce perioperative stroke severity in high-risk elective vascular surgery.
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