Technical Abstract: Cognitive impairment in age-related neurodegenerative diseases such as Alzheimer's Disease may be due in part to long-term exposure and increased susceptibility to inflammatory insults. This study investigated whether the polyphenols in blueberries (BBs) can reduce the deleterious effects of inflammation, perhaps by increasing anti-inflammatory protection in the brain and/or reducing brain susceptibility to inflammatory insults. Therefore, 4 month old male F344 rats were fed a control, 2% BB, or 0.015% piroxicam (PX, an NSAID) diet for 8 weeks before Ringers (R) or kainic acid (KA, 300ng in 0.5ul R) was injected bilaterally into the hippocampus. Ten days later, rats were tested for 4 days in the Morris water maze before measuring brain inflammatory markers. KA produced an inflammatory response as shown by increased OX-6 activation in the hippocampus, and had deleterious effects on cognitive behavior. Specifically, rats on the control diet given KA had increased latencies to find the hidden platform in the MWM on days 1-3, and on day 4 during reversal learning, compared to the R group. These deficits were improved by the BB diet; latencies to find the platform on days 2-4 in the BB-KA group were not different than the control diet-R group. Also, the KA group utilized non-spatial strategies during the probe trials on days 2-4: i.e., longer latencies to, fewer crossings of and less time spent in the previous platform location. The BB diet, and to a lesser degree the PX diet, was able to improve performance on probe trial measures. Interestingly, both the BB and PX diet were able to improve performance in the rats administered R on some measures. These results indicate that BB polyphenols have anti-inflammatory actions, comparable to or greater than PX. (Supported by USDA Intramural & Alzheimer Assoc)