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Regional Neurodegeneration and Gliosis Are Amplified by Mild Traumatic Brain Injury Repeated at 24-Hour Intervals
Open accessAbstract
Most traumatic brain injuries (TBIs) that occur every year are classified as "mild." Individuals involved in high-risk activities may sustain multiple mild TBIs. We evaluated the acute physiologic and histopathologic consequences of mild TBI in a mouse model, comparing sham injury, single impact, or 5 impacts at a 24- or 48-hour interinjury interval. A single closed skull impact resulted in bilateral gliosis in the hippocampus and entorhinal cortex that was proportional to impact depth. Midline impact, at a depth just above the threshold to induce transient unconsciousness, produced occasional axonal injury and degenerating neurons accompanied by astrogliosis in the entorhinal cortex and cerebellum. Mild TBI repeated every 24 hours resulted in bilateral hemorrhagic lesions in the entorhinal cortex along with significantly increased neurodegeneration and microglial activation despite diminished durations of apnea and unconsciousness with subsequent impacts. Astrogliosis and diffusely distributed axonal injury were also observed bilaterally in the cerebellum and the brainstem. When the interval between mild TBIs was increased to 48 hours, the pathologic consequences were comparable to those of a single TBI. Together, these data suggest that, in mice, the brain remains at an increased risk for damage for 24 hours after mild TBI despite reduced acute physiologic responses to subsequent mild impacts.
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“This suggests the presence of incremental gliosis and microglial activation, two well-researched and reproducible repercussions of the mild injury model used in this study [9].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [9]
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Metadata
- Authors
- Bolton, A. N., & Saatman, K. E.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Saatman, Kathryn E.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10
- Volume
- 73
- Issue
- 10
- Pages
- 933-947
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC4170569
- OpenAlex
- W2330807792
- Cited by
- 86
- References
- 50
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 15 · 2018: 10 · 2017: 10 · 2016: 12 · 2015: 7
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS058484, P30NS051220, T32NS077889)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
- Keywords
- mild traumatic brain injury, astrocyte activation, microglial activation, axonal injury, entorhinal cortex, hippocampus, cerebellum, hemorrhagic lesions, impact depth, mouse model
- MeSH terms
- Animals, Brain Injuries, Gliosis, Male, Mice, Inbred C57BL, Nerve Degeneration, Time Factors, Mice
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