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Cited by 51Alzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury Research

Traumatic brain injury reduces soluble extracellular amyloid-β in mice: A methodologically novel combined microdialysis-controlled cortical impact study

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Schwetye, Katherine E., Cirrito, John R., Esparza, Thomas J., Mac Donald, Christine L., Holtzman, David M., Brody, David L.·2010·Neurobiology of Disease
DOI 10.1016/j.nbd.2010.06.018PMC PMC2955836
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Abstract

Acute 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.

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  • Urea has been utilized as an independent measure of probe function and recovery in both human and animal brain microdialysis studies.

    “Since the metabolite urea has been utilized as an independent measure of probe function and recovery in both human and animal brain microdialysis studies (34-37)”

    From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [37]

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Authors
Schwetye, K. E., Cirrito, J. R., Esparza, T. J., Mac Donald, C. L., Holtzman, D. M., & Brody, D. L.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Brody, David L.
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2010-12
Volume
40
Issue
3
Pages
555-564
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2010.06.018
PMC
PMC2955836
OpenAlex
W2060286035
Cited by
51
References
7
Citations by year
2026: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 6 · 2012: 6
FWCI
4.33
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
NIH (NS049237, AG13956)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
traumatic brain injury, amyloid-beta, microdialysis, controlled cortical impact, hippocampus, Tg2576 mice, PDAPP mice, neuronal activity, electroencephalographic activity, dementia risk, transgenic mouse model
MeSH terms
Animals, Brain Injuries, Disease Models, Animal, Electroencephalography, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Amyloid beta-Peptides, Microdialysis, Extracellular Fluid, Mice

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