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Cited by 111Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchAutomotive and Human Injury Biomechanics

Cytoskeletal protein degradation and neurodegeneration evolves differently in males and females following experimental head injury

Kupina, Nancy C, Detloff, Megan R, Bobrowski, Walter F, Snyder, Bradley J, Hall, Edward D·2003·Experimental Neurology
DOI 10.1016/s0014-4886(02)00048-1
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Abstract

The resulting neuropathological degeneration that occurs following a traumatic brain injury (TBI) is a consequence of both immediate and secondary neurochemical sequelae. Proteolysis of cytoskeletal proteins, triggered by calcium-mediated events, is believed to be a particularly significant contributor to TBI-induced neuronal death. To date, efforts to associate cytoskeletal degradation and neurodegeneration in TBI have been primarily qualitative or semiquantitative. The objectives of this study were (1). to quantitatively describe, over a posttraumatic time course, the relationship and mechanisms of cytoskeletal degradation (Western blot) and neurodegeneration (silver staining) in male and female mice following a moderately severe weight-drop impact-acceleration head injury; (2). to evaluate gender differences in the response to TBI; and (3). to examine the potential therapeutic window for future pharmacological treatment strategies. In male and female mice, we report a close correlation in the time courses of neurofilament M protein degradation and alpha-spectrin breakdown products (SBDP 150 and 145) with the peak magnitude of neurodegeneration, as quantified by silver staining. Evidence from the increased patterns of SBDPs suggests that both calpain and caspase-3 are involved. In general, males incurred peak protein degradation and neurodegeneration within 3 days after injury, while in females this did not occur until 14 days. The neuroprotective effects of estrogen are believed to be key factors in the superior outcome of female vs male mice following TBI. In mice, the therapeutic window of opportunity for pharmacological intervention aimed at limiting cytoskeletal degradation might be as much as 24 h following injury. Evidence of a protracted time course of cytoskeletal degradation, especially in females, suggests a potential for an extended treatment-duration following TBI.

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  • Impact acceleration injury resulted in an earlier peak of neurodegeneration in male mice (3 days) versus a 14-day peak in females.

    “Impact acceleration injury also resulted in an earlier peak of neurodegeneration in male mice (3 days) versus a 14-day peak in females. 42”

    From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [42]

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Authors
Kupina, N. C., Detloff, M. R., Bobrowski, W. F., Snyder, B. J., & Hall, E. D.
Affiliations
Pfizer (United States) (US)
Corresponding author
Hall, Edward D
ORCID
Detloff, Megan R
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2003-03
Volume
180
Issue
1
Pages
55-73
ISSN
0014-4886 (ISSN-L)
DOI
10.1016/s0014-4886(02)00048-1
OpenAlex
W2007922486
Cited by
111
References
84
Citations by year
2026: 1 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 9
FWCI
5.63
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
Keywords
traumatic brain injury, neurodegeneration, sex differences, neurofilament M, calpain, caspase-3, estrogen neuroprotection, therapeutic window, neuronal cell death
MeSH terms
Animals, Brain, Brain Injuries, Cerebral Cortex, Corpus Striatum, Cytoskeletal Proteins, Densitometry, Disease Models, Animal, Female, Hippocampus, Male, Sex Factors, Spectrin, Time Factors, Survival Rate, Silver Staining, Neurofilament Proteins, Disease Progression, Neurodegenerative Diseases, Mice

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