Abstract W P250: Food Restriction Ameliorates Neuroinflammation and Provides Protection in a Mouse Model of Ischemic Stroke

Abstract

Background and Purpose: Neuroinflammation contributes significantly to the progress of ischemic stroke. Recent research suggests that food restriction could reduce inflammatory responses under some pathological conditions. In this study, we demonstrate that food restriction attenuates both grey matter and white matter damage after cerebral ischemia. Methods: Adult male C57BL/6 mice were fed ad libitum (AL) or fed with restricted food (RF; 30% reduction) for 28 days, and then subjected to MCAO or sham operation. Neuronal tissue atrophy and white matter injury were assessed by quantifying the expression of microtubule-associated protein (MAP2) and myelin basic protein (MBP), respectively. Cerebral inflammation was evaluated by immunohistochemical staining of astrocyte and microglia in the ischemic brain. The expression of M1 and M2 markers were further examined to characterize phenotypic changes in brain microglia. Results: RF promotes functional recovery up to 28 days after stroke, as revealed by marketly improved performance in food fault test, cylinder test and Morris water maze test. RF mice exhibited significantly reduced neuronal tissue loss (AL, 19.43±2.40mm3; RF, 10.60±1.74mm3; P < 0.05;n=6/group) and white matter injury (Al,, 0.36±0.08; RF, 0.97±0.07; P < 0.05;n=5/group) as compared to AL mice at 28 days after ischemia. Meanwhile, we observed suppressed astrocyte (LF, 3.22±0.26mm2; RF, 2.30±0.19mm2; P < 0.05;n=5/group) and microglia (P < 0.05;n=5/group) activation in RF mice. Furthermore, food restriction increased the percentage of M2 phenotype and reduced the percentage of M1 phenotype in activated microglia (P < 0.05;n=5/group). Conclusions: Taken together, food restriction can promote functional recovery. These protective effects might be partially attributed to the effect of food restriction in alleviating neuroinflammation and directing beneficial microglial response after stroke. Our study suggests that food restriction is an effective non-pharmacological approach to promote long-term post-stroke recovery.