Short-term preoperative dietary restriction is neuroprotective in a rat focal stroke model.
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.
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Kärt
K
Varendi
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Mikko
M
Airavaara
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Jenni
J
Anttila
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Sarah
S
Vose
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Anu
A
Planken
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Mart
M
Saarma
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
James R
JR
Mitchell
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Jaan-Olle
JO
Andressoo
D000818:Animals; D001786:Blood Glucose; D016207:Cytokines / Q000097:blood; D018753:Diet, Protein-Restricted; D005215:Fasting; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D057234:Preoperative Period; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D020521:Stroke / Q000473:pathology* / Q000517:prevention & control* / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001786:Blood Glucose; D016207:Cytokines; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1