A compelling body of literature suggests berry phytochemicals play beneficial roles in reversing age-related cognitive impairment and protect against neurodegenerative disorders. Anthocyanins are bioactive phytochemicals in berries suspected to be responsible for some of these neuroprotective effects. The plausible mechanisms of anthocyanin bioactivity in brain tissue are dependent on their bioavailability to the brain. Pigs were fed 2% whole freeze-dried, powdered blueberry in the diet for 8 weeks. Anthocyanin and anthocyanin glucuronides were measured in the cortex, cerebellum, and midbrain and diencephalon by LC-MS/MS. Anthocyanins and their glucuronides were found in the range of femtomoles per gram of fresh weight of tissue at 18 h postprandial, after anthocyanins had been removed from the blood by xenobiotic metabolism. Xenobiotic metabolism, anthocyanin interaction, and transporter barriers to brain bioavailability are briefly discussed. The plausible mechanism of neuroprotective action of anthocyanins may be via modulation of signal transduction processes and/or gene expression in brain tissue rather than by direct antioxidant radical quenching.