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

Journal of Neuroinflammation

Catherine B Lawrence³  Barry W McColl¹  Siddharth Krishnan³  Natalia Gorenkova³  Michael J. Haley³  Samaneh Maysami² 

[1] The Roslin Institute and R(D)SVS, University of Edinburgh Easter Bush, Midlothian EH25 9RG, UK;Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK;Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK

关键词: Neutrophils;    Chemokines;    Stroke;    Cerebral ischaemia;    Diet-induced obesity;   

Others  :  1221902
DOI  :  10.1186/s12974-015-0359-8

 received in 2015-02-19, accepted in 2015-07-03,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Maysami et al.

【 图 表 】

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