Short-term preoperative dietary restriction is neuroprotective in a rat focal stroke model

PLoS One. 2014 Apr 4;9(4):e93911. doi: 10.1371/journal.pone.0093911. eCollection 2014.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Cytokines / blood
  • Diet, Protein-Restricted*
  • Fasting*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Neuroprotective Agents / pharmacology*
  • Preoperative Period*
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Stroke / pathology*
  • Stroke / prevention & control*
  • Stroke / surgery
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Blood Glucose
  • Cytokines
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1