Abstract 5: Indirect Brain Injury Resulting from Severe Burns Results in Estrogen-Reversible Elevations of Markers of Alzheimer's Disease
Background: Prior studies have found that patients with severe burns may suffer neurocognitive changes. While frequently attributed to psycho-social issues, recent data from our lab revealed a substantial, rapid and sustained (30 min - 7 day) increase in rat brain inflammation following burns that is blunted by a single post-burn dose of estrogen. Other brain injury processes, such as TBI and stroke have shown an accelerated accumulation of Aβ40, Aβ42, and pTau, leading to a clinical picture of early Alzheimer's disease (AD). We hypothesized that similar AD processes may be triggered in severe burn injury, and altered by post-burn estrogen.
Methods: 149 male rats were given a 3° 40% TBSA scald burn. Rats were randomized into 3 groups: Group 1 (0.5mg/kg of 17β estradiol (E2) 15 min after injury); Group 2 (placebo); and Group 3 (sham-burn control). These rats were sequentially sacrificed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24 hours post-burn. An additional 24 rats were sacrificed 7 days post-burn. Brain tissue IL-6, Aβ40, Aβ42, and pTau were measured using ELISA.
Results: Compared to placebo, early estrogen treatment significantly decreases (~90%) brain levels of IL-6 at all measured time points. At 7 days post-burn, rats receiving E2 exhibited similar Aβ40, Aβ42, and pTau to the unburned group, while those receiving placebo were significantly elevated.
Conclusions: 17β estradiol not only mitigates the early-onset, sustained brain inflammation following burn injury in a rat model, but also significantly decreases brain levels of Aβ40, Aβ42, and pTau. We hypothesize that other injuries causing acute, remote brain inflammation (such as cardiac arrest) may trigger similar AD-like brain changes.
- © 2011 by American Heart Association, Inc.