Varendi, KärtAiravaara, MikkoAnttila, JenniVose, SarahPlanken, AnuSaarma, MartMitchell, JamesAndressoo, Jaan-Olle2014-05-062014Varendi, Kärt, Mikko Airavaara, Jenni Anttila, Sarah Vose, Anu Planken, Mart Saarma, James R. Mitchell, and Jaan-Olle Andressoo. 2014. “Short-term Preoperative Dietary Restriction Is Neuroprotective in a Rat Focal Stroke Model.” PLoS ONE 9 (4): e93911. doi:10.1371/journal.pone.0093911. http://dx.doi.org/10.1371/journal.pone.0093911.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152880Stroke 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.en-USBiology and Life SciencesNeuroscienceBehavioral NeuroscienceMedicine and Health SciencesCardiologyHealth CareHealth Care PolicyTreatment GuidelinesMental Health and PsychiatryNeurologyCerebrovascular DiseasesSurgical and Invasive Medical ProceduresCardiovascular ProceduresVascular MedicineStrokeIschemic StrokeAnimal Models of DiseaseModel OrganismsAnimal ModelsClinical Research DesignPreclinical ModelsJournal Article2014-05-0610.1371/journal.pone.0093911