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.
Highlights
Perioperative stroke occurring during or soon after surgery is a major cause of morbidity and mortality, with an average incidence of 2–13% in cardiovascular procedures and 0.08–0.7% in noncardiovascular procedures [1,2]
While global brain hypoperfusion accounts for less than 10% of perioperative strokes in humans [2], the majority (62%) of perioperative strokes are caused by focal ischemic insults that are mechanistically and pathologically different from hypoperfusion
Unlike long-term Dietary restriction (DR), we found no significant differences in mRNA expression levels of growth factor-related, cytoprotective or pro-inflammatory markers at baseline as a result of 3d of fasting relative to ad libitum (AL) fed controls (Fig 2B, Table S1). 24hr after reperfusion, expression of mRNAs encoding for the pro-inflammatory cytokine tumor necrosis factor alpha (TNFa), its receptor TNFRSF1A and its downstream target, the intercellular adhesion molecule 1 (ICAM1) were significantly upregulated in the lesioned hemisphere compared to the control hemisphere in the ad libitum group, but not in the fasted group (Fig 2C), suggesting attenuation of the inflammatory response to stroke in fasted rats
Summary
Perioperative stroke occurring during or soon after surgery is a major cause of morbidity and mortality, with an average incidence of 2–13% in cardiovascular procedures and 0.08–0.7% in noncardiovascular procedures [1,2]. With 7 million cardiovascular and 21 million non-cardiovascular surgeries performed annually in the US [3] and similar numbers in Europe (extrapolated from data from the Netherlands [4]), annual deaths are calculated to be in excess of 180,000 on these two continents alone. Those left with the debilitating consequences of perioperative stroke/encephalopathy number an order of magnitude higher [5,6]. While perioperative stroke risk assessment prior to surgery is a common practice, general prophylactic methods are lacking [1,2], underpinning a need for basic research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
