The Impact of Protein-Energy Malnutrition after Stroke on Recovery of Walking in Rats

Abstract

Understanding comorbidity factors is essential for optimal stroke recovery. Up to 49% of patients develop protein-energy malnutrition (PEM) after stroke, but its effects have not been adequately addressed. The study objectives were to determine the effects of post-stroke PEM on the recovery of skilled locomotion and infarct size. Adult, male (12-week-old) Sprague-Dawley rats were trained to walk on a regular rung pattern in the horizontal ladder and tested prior to surgery to establish pre-stroke baseline. Rats (now 16 weeks old) were assigned to photothrombotic stroke targeting the forelimb motor cortex or sham surgery. On day 2, rats were tested on the regular ladder rung pattern before assignment to control (12.5% protein) or low protein (0.5%) diets and subdivision into subacute (studied until day 12) or chronic (day 28) groups (n=6-10/group/study). On day 11, rats were tested on the regular pattern and a novel irregular pattern. Chronic study rats were tested again on day 27 on the regular and (no longer novel) irregular patterns. Food intake and body weight were monitored. Serum albumin concentration was measured by a spectrophotometric assay and liver lipid was measured by lipid extraction and dry lipid weight. Infarct volume was measured on cresyl violet stained brain sections. Feeding the low protein diet resulted in PEM by day 12, based on a decrease in body weight (ANOVA; p<0.030), daily food intake (p<0.019) and serum albumin concentration (p<0.001). A trend for increased liver lipid content in PEM rats became evident on day 28 (p=0.051). On the ladder regular pattern, stroke increased error rate only on day 2 (repeated measures ANOVA; p<0.001). On the irregular rung pattern, stroke rats had higher error rates relative to shams on days 11 and 27 (p<0.009). PEM rats exposed to stroke had more errors than the other groups when the irregular pattern data on d11 were combined from both studies (p<0.007). PEM did not alter infarct size on day 12 or 28 (t-test; p>0.05). In conclusion, post-stroke PEM worsened recovery on only the most challenging and novel walking task. Since infarct size was unaltered, other mechanisms are hypothesized to underlie the functional effects.