Severe Remote Burn Injury Results in Early, Elevated Markers of Alzheimer's Disease
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BACKGROUND: Prior studies have found that patients with severe burns may suffer neurocognitive decline. While these observations are frequently attributed to psycho-social causes, our lab recently reported that remote burn injury is associated with significant brain changes, including new data revealing a substantial, rapid and sustained (30 min - 45 day) increase in rat brain inflammation following remote burns. Other acute brain injury processes, such as traumatic brain injury and stroke have been associated with an accelerated accumulation of Aβ40, Aβ42,, and Tau, and ultimately a clinical picture of early-onset Alzheimer's disease (AD). We hypothesized that similar AD-like processes may be triggered in the brain following remote, severe burn injury. METHODS: In this study, 44 male rats received a 3° 40% TBSA back/flank scald burn by immersion (divided into 6 harvest time points), with an additional 8 receiving a sham burn (immersion in room temperature water), totaling 52 rats. Brains of those burned were harvested at 1, 6, 12, 24 hours, 7 days (n=8/each time point) and 45 days (n=4/time point) after injury. Brain tissue IL-6, TNF-α, IL-1β, Aβ40, Aβ42, total Tau and phosphorylated Tau were measured using ELISA methods. RESULTS: Burned animals had significantly increased markers of inflammation and AD at each time point measured compared with those receiving a sham burn injury (see table for data at 1 hour and 45 days). CONCLUSIONS: Severe remote burn injury not only results in early, robust, and sustained neuroinflammation, but also significantly increases brain levels of Aβ40, Aβ42, and Tau. This novel finding may pave the way for future brain-preserving interventional trials in burn patients, as well as provide a more rapid and effective testing-ground for new therapies aimed at slowing and/or preventing AD.