title: Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke.
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.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK.|Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Maysami
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Haley
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gorenkova
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh Easter Bush, Midlothian, EH25 9RG, UK.
authors.forename: Barry W
authors.initials: BW
authors.lastname: McColl
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK. catherine.lawrence@manchester.ac.uk.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D011379:Prognosis; D011897:Random Allocation; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D018925:Chemokines