• Katherine E Schwetye, John R Cirrito, Thomas J Esparza, Christine L Mac Donald, David M Holtzman, and David L Brody.
• Washington University School of Medicine, Department of Neurology and Hope Center for Neurological Disorders, 660 S. Euclid Ave Box 8111, St. Louis, MO 63110, USA.
• Neurobiol. Dis. 2010 Dec 1;40(3):555-64.

AbstractAcute amyloid-β peptide (Aβ) deposition has been observed in young traumatic brain injury (TBI) patients, leading to the hypothesis that elevated extracellular Aβ levels could underlie the increased risk of dementia following TBI. However, a recent microdialysis-based study in human brain injury patients found that extracellular Aβ dynamics correlate with changes in neurological status. Because neurological status is generally diminished following injury, this correlation suggested the alternative hypothesis that soluble extracellular Aβ levels may instead be reduced after TBI relative to baseline. We have developed a methodologically novel mouse model that combines experimental controlled cortical impact TBI with intracerebral microdialysis. In this model, we found that Aβ levels in microdialysates were immediately decreased by 25-50% in the ipsilateral hippocampus following TBI. This result was found in PDAPP, Tg2576, and Tg2576-ApoE2 transgenic mice producing human Aβ plus wild-type animals. Changes were not due to altered probe function, edema, changes in APP levels, or Aβ deposition. Similar decreases in Aβ were observed in phosphate buffered saline-soluble tissue extracts. Hippocampal electroencephalographic activity was also decreased up to 40% following TBI, and correlated with reduced microdialysate Aβ levels. These results support the alternative hypothesis that post-injury extracellular soluble Aβ levels are acutely decreased relative to baseline. Reduced neuronal activity may contribute, though the underlying mechanisms have not been definitively determined. Further work will be needed to assess the dynamics of insoluble and oligomeric Aβ after TBI.Copyright © 2010 Elsevier Inc. All rights reserved.

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