Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice
Abstract
Extensive tau-immunoreactive neurons and glial cells associated with chronic traumatic encephalopathy (CTE) have been documented in the brains of some professional athletes and others with a history of repetitive mild traumatic brain injury (r-mTBI). The neuropathology and tau involvement in mTBI have not been extensively studied in animal models, particularly in aged animals. We investigated the effects of single mTBI (s-mTBI) and r-mTBI in 18-month-old hTau mice, which express wild-type human tau isoforms on a null murine tau background (n = 3-5 per group). At this age, hTau mice already demonstrate tau pathology, but there was a significant increase in phospho-tau immunoreactivity in response to r-mTBI, but not to s-mTBI,as determined using multiple phospho-tau-specific antibodies. Repetitive mTBI also resulted in a marked increase in astrocyte/microglia activation notably in the superficial layer of the motor/somatosensory cortex and the corpus callosum. We did not observe the perivascular tau pathology, neuritic threads, or astrocytic tangles that are commonly found in human CTE. The increase in phospho-tau in the r-mTBI mice suggests that this may be a useful model for investigating further the link between mTBI, particularly r-mTBI, and tau pathobiology in CTE and in understanding responses of the aged brain to mTBI.
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Only transgenic tau mouse models [T44 (one mouse), hTau] displayed NFT pathology following repetitive TBI.
“Similarly, only transgenic tau mouse models [T44 (one mouse), hTau] displayed NFT pathology following repetitive TBI (153, 234).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [153]
Chronic neuroinflammation could provoke tau pathology thereby worsening neuronal injury and long-term outcome.
“Together, these studies indicate that chronic neuroinflammation could provoke tau pathology thereby worsening neuronal injury and long-term outcome.”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [153]
Macrophage reactivity was only reported in 1 of these 4 studies, and indicated that repetitive TBI in aged hTau mice resulted in increased CD45 immunoreactivity in the cortex, corpus callosum, and hippocampus 3 weeks post-injury.
“Macrophage reactivity was only reported in 1 of these 4 studies, and indicated that repetitive TBI in aged hTau mice resulted in increased CD45 immunoreactivity in the cortex, corpus callosum, and hippocampus 3 weeks post-injury (153).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [153]
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- Authors
- Ojo, J.-O., Mouzon, B., Greenberg, M. B., Bachmeier, C., Mullan, M., & Crawford, F.
- Affiliations
- Roskamp Institute (US)
- Corresponding author
- Ojo, Joseph-Olubunmi
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02
- Volume
- 72
- Issue
- 2
- Pages
- 137-151
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2319236841
- Cited by
- 166
- References
- 15
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 13 · 2023: 7 · 2022: 4 · 2021: 14 · 2020: 11 · 2019: 16 · 2018: 16 · 2017: 13 · 2016: 17 · 2015: 21 · 2014: 14 · 2013: 9 · 2012: 1
- FWCI
- 14.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH1010759, W81XWH)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- repetitive mild traumatic brain injury, chronic traumatic encephalopathy, tau pathology, phosphorylated tau, glial activation, astrocyte activation, microglial activation, brain aging, corpus callosum, animal models
- MeSH terms
- Age Factors, Animals, Epitopes, Brain Injuries, Disease Models, Animal, DNA-Binding Proteins, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Humans, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Neuroglia, Neurons, Transcription Factors, tau Proteins, Apoptosis, Leukocyte Common Antigens, In Situ Nick-End Labeling, Tauopathies, Mice, Polycomb-Group Proteins
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