• David J Loane, Patricia M Washington, Lilit Vardanian, Ana Pocivavsek, Hyang-Sook Hoe, Karen E Duff, Ibolja Cernak, G William Rebeck, Alan I Faden, and Mark P Burns.
• Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
• J. Neurotrauma. 2011 Feb 1; 28 (2): 225236225-36.

AbstractTraumatic brain injury (TBI) increases brain beta-amyloid (Aβ) in humans and animals. Although the role of Aβ in the injury cascade is unknown, multiple preclinical studies have demonstrated a correlation between reduced Aβ and improved outcome. Therefore, therapeutic strategies that enhance Aβ clearance may be beneficial after TBI. Increased levels of ATP-binding cassette A1 (ABCA1) transporters can enhance Aβ clearance through an apolipoprotein E (apoE)-mediated pathway. By measuring Aβ and ABCA1 after experimental TBI in C57BL/6J mice, we found that Aβ peaked early after injury (1-3 days), whereas ABCA1 had a delayed response (beginning at 3 days). As ABCA1 levels increased, Aβ levels returned to baseline levels-consistent with the known role of ABCA1 in Aβ clearance. To test if enhancing ABCA1 levels could block TBI-induced Aβ, we treated TBI mice with the liver X-receptor (LXR) agonist T0901317. Pre- and post-injury treatment increased ABCA1 levels at 24 h post-injury, and reduced the TBI-induced increase in Aβ. This reduction in Aβ was not due to decreased amyloid precursor protein processing, or a shift in the solubility of Aβ, indicating enhanced clearance. T0901317 also limited motor coordination deficits in injured mice and reduced brain lesion volume. These data indicate that activation of LXR can reduce Aβ accumulation after TBI, and is accompanied by improved functional recovery.

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