Effect of protein-energy malnutrition on nuclear factor kappa B activation following global ischemia

Abstract

Our laboratory previously found that protein-energy malnutrition (PEM) existing prior to brain ischemia impaired functional outcome measured in an open field test, and one-third of animals showed a marked increase in reactive gliosis. It was hypothesized that PEM worsened stroke outcome by increasing inflammation via increased activation of the transcription factor, nuclear factor kappa B (NFκB). Mongolian gerbils (11-12 wk old) were randomly assigned to a control diet (12.5% protein) or a protein-deficient diet (2%) for 28 days. The control group on average gained 4.9g and the PEM group lost 7.4g. PEM gerbils had significantly decreased food intake (P <0.001; unpaired t-test). Animals were then subjected to global ischemia or sham surgery, resulting in four experimental groups. Global ischemia was achieved by a 5 min bilateral common carotid artery occlusion with tympanic temperature regulated at 36.5 ± 0.2°C. PEM independently increased hippocampal NFκB activation by three times higher than control diet animals at 6hr after surgery (p=0.014; 2-factor ANOVA) detected by electrophoretic mobility shift assay (EMSA). There was no significant effect of ischemia on NFκB activation and there was no interaction of diet and ischemia. Serum glucose and serum cortisol were also measured since both variables can be affected by PEM and can influence stroke outcome, but there was no significant effect of diet or ischemia. Because of the increased NFκB activation observed in PEM-Sham animals, a second experiment investigated if PEM also increased NFκB activation in the absence of surgery. Gerbils of the same age were randomly assigned to either control diet or PEM for 28 days but did not receive any surgery. PEM consistently increased NFκB activation. Since PEM exists in 16% of elderly stroke patients at admission, the data suggest that PEM may worsen stroke outcome through increased activation of NFκB. Because increased NFκB activation was also observed in PEM independent of ischemia, the data also have implications for the inflammatory response of protein-energy malnourished elderly in general.