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Cited by 151Traumatic Brain Injury ResearchTraumatic Brain Injury and Neurovascular DisturbancesAutomotive and Human Injury Biomechanics

The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy.

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Petraglia, AnthonyL, Plog, BenjaminA, Dayawansa, Samantha, Dashnaw, MatthewL, Czerniecka, Katarzyna, Walker, CoreyT, Chen, Michael, Hyrien, Ollivier +4 more·2014·Surgical Neurology International
DOI 10.4103/2152-7806.147566PMC PMC4287910
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Abstract

BACKGROUND: An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. METHODS: Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. RESULTS: Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. CONCLUSIONS: The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.

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  • Tau hyperphosphorylation is consistently present in the initial and long-term secondary mechanisms initiated by traumatic brain injury.

    “Tau hyperphosphorylation is also consistently present in the initial and long-term secondary mechanisms initiated by traumatic brain injury (TBI) (Petraglia et al., 2014; Zheng et al., 2014; Rubenstein et al., 2015; Ali et al., 2019; Tan et al., 2020), a leading cause of morbidity and mortality worldwide (Hay et al., 2016).”

    From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Petraglia et al., 2014

    The Results (Figure 4) report increased phosphorylated tau at 7 days and 1 month after both single and repetitive mild TBI, persisting at 6 months only after repetitive injury. The Discussion (Figure 6) says the increase after a single mild TBI clears by 6 months. Thus the paper supports early and long-term tau changes in its mouse model, but not their consistent long-term presence after TBI generally. (LLM, conf=0.88)

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Authors
Petraglia, A., Plog, B., Dayawansa, S., Dashnaw, M., Czerniecka, K., Walker, C., Chen, M., Hyrien, O., Iliff, J., Deane, R., Huang, J., & Nedergaard, M.
Affiliations
University of Rochester Medicine (US)
ORCID
Venue
Surgical Neurology International
Publisher
Scientific Scholar
Published
2014
Volume
5
Issue
1
Pages
184
ISSN
2152-7806 (ISSN-L)
DOI
10.4103/2152-7806.147566
PMC
PMC4287910
OpenAlex
W2134478490
Cited by
151
References
70
Citations by year
2026: 7 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 11 · 2021: 17 · 2020: 14 · 2019: 14 · 2018: 15 · 2017: 22 · 2016: 16 · 2015: 12 · 2014: 1
FWCI
12.88
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Surgical Neurology International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Novo Nordisk Fonden (NNF13OC0004258)
  • National Institutes of Health (UL1TR000042)
  • National Institute of Neurological Disorders and Stroke (R01NS078167, R01NS075177, R25NS065748, R01NS067435)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
Keywords
chronic traumatic encephalopathy, repetitive mild traumatic brain injury, mouse model, astrocyte activation, microglial activation, tau hyperphosphorylation, neuroinflammation, reactive astrocytes, neurodegeneration

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