Abstract WP114: High-fat Diet Leads to Increased Brain Inflammation and Worse Outcomes After Stroke in Mice

Abstract

People who are obese are 64% more likely to have a stroke than those who are not. Obesity is also associated with chronic peripheral inflammation characterized by increased antigen presentation and pro-inflammatory T lymphocytes. The influence of obesity-induced peripheral inflammation on stroke outcomes has not been well studied. We hypothesized that a similar mechanism might drive detrimental inflammation after stroke in mice and lead to worse outcomes. We fed mice a 60% kCal high fat diet for six or fifteen weeks and measured the neuroinflammatory response to stroke. We verified weight changes and measured the neuroinflammatory response, infarct size, and functional outcomes following stroke (dMCAO & photothrombotic). Animals were fed a high fat diet or control diet for either 6 or 15 weeks (N = 10/group) that resulted in 36% and 78% more weight gain, respectively. Consistent with a stronger innate inflammatory response, we found increased astrogliosis (195%; p < 0.01) with GFAP immunostaining and microgliosis (290%; p < 0.0001) with CD68 in the peri-infarct area, as well as higher expression of the pro-inflammatory cytokines TNFα ( p < 0.05) and IL-6 ( p < 0.05). Similar to the increased adaptive immune responses in adipose tissue of the obese, we saw a significant ( p < 0.05) increase in MHC II+ cells in the peri-infarct area as well as a 2 fold increase ( p < 0.05) in the number of infiltrating CD3+ T-cells in the hemisphere ipsilateral to the stroke, at both 3 days and 28 days post-stroke. Animals on high fat diet had a significantly ( p < 0.01) larger dMCAO infarct (130%) size 3 days post-stroke than animals on control diet. To determine the effect this neuroinflammatory response had on outcome mice received photothrombotic stroke over the motor cortex and were motor testing was performed prior to and 1, 3, 7, 14, and 28 days post-stroke. Mice fed a high fat diet performed significantly ( p < 0.05) worse on both the rotating and tapered beam tasks, and also exhibited larger strokes at sacrifice. We conclude that eating a high fat diet prior to stroke increases neuroinflammation, infarct size, and functional recovery following stroke.