Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke

Background: obesity increases the risk for ischaemic stroke and is associated with worse outcome clinically and experimentally. most experimental studies have used genetic models of obesity. here,a more clinically relevant model,diet-induced obesity,was used to study the impact of obesity over time on the outcome and inflammatory response after stroke. methods: male c57bl/6 mice were maintained on a high-fat (60 % fat) or control (12 % fat) diet for 2,3,4 and 6 months when experimental stroke was induced by transient occlusion of the middle cerebral artery (mcao) for either 20 (6-month diet) or 30 min (2-,3-,4- and 6-month diet). ischaemic damage,blood-brain barrier (bbb) integrity,neutrophil number and chemokine expression in the brain were assessed at 24 h. plasma chemokine levels (at 4 and 24 h) and neutrophil number in the liver (at 24 h) were measured. physiological parameters (body weight and blood glucose) were measured in naïve control- and high-fat-fed mice at all time points and blood pressure at 3 and 6 months. blood cell counts were also assessed in naïve 6-month control- and high-fat-fed mice. results: mice fed a high-fat diet for 6 months had greater body weight,blood glucose and white and red blood cell count but no change in systolic blood pressure. after 4 and 6 months of high-fat feeding,and in the latter group with a 30-min (but not 20-min) occlusion of the mca,obese mice had greater ischaemic brain damage. an increase in blood-brain barrier permeability,chemokine expression (cxcl-1 and ccl3),neutrophil number and microglia/macrophage cells was observed in the brains of 6-month high-fat-fed mice after 30-min mcao. in response to stroke,chemokine (cxcl-1) expression in the plasma and liver was significantly different in obese mice (6-month high-fat fed),and a greater number of neutrophils were detected in the liver of control but not obese mice. conclusions: the detrimental effects of diet-induced obesity on stroke were therefore dependent on the severity of obesity and length of ischaemic challenge. the altered inflammatory response in obese mice may play a key role in its negative impact on stroke. © 2015 maysami et al.