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

Maysami, S; Haley, MJ; Gorenkova, N; Krishnan, S; McColl, BW; Lawrence, CB

Abstract

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.

Citation

Maysami, S., Haley, M., Gorenkova, N., Krishnan, S., McColl, B., & Lawrence, C. (2015). Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke. Journal of Neuroinflammation, 140 - ?. https://doi.org/10.1186/s12974-015-0359-8

• Acceptance Date: Jul 3, 2015
• Publication Date: Aug 4, 2015
• Journal: Journal of Neuroinflammation
• Publisher: Springer Verlag
• Pages: 140 - ?
• DOI: https://doi.org/10.1186/s12974-015-0359-8
• Keywords: Diet-induced obesity, Cerebral ischaemia, Stroke, Chemokines, Neutrophils
• Publisher URL: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0359-8#article-info