Cited by 440Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchAutomotive and Human Injury Biomechanics

Progressive atrophy and neuron death for one year following brain trauma in the rat

Smith, Douglas H., Chen, Xiao-Han, Pierce, Jean E. S., Wolf, John A., Trojanowski, John Q., Graham, David I., McIntosh, Tracy K.·1997·Journal of Neurotrauma

Abstract

Although atrophic changes have been well described following traumatic brain injury (TBI) in humans, little is known concerning the mechanisms or progression of brain tissue loss. In the present study, we evaluated the temporal profile of histopathological changes following parasagittal fluidpercussion (FP) brain injury in rats over 1 year postinjury. Anesthetized 3-4 month-old SpragueDawley Rats ( n = 51) were subjected to FP brain injury of high severity (2.5–2.9 atm, n = 51) or sham treatment ( n = 27). At 1 h, 2 h, 48 h, 1 week, 2 weeks, 1 month, 2 months, 6 months and 1 year after brain injury or sham treatment, these animals were humanely euthanized. Brain sections were analyzed with image-processing techniques to determine the extent of cortical tissue loss and shrinkage of the hippocampal pyramidal cell layer. In addition, cell counting was performed to determine the number of neurons in the dentate hilus of the hippocampus, and glial fibrillary acidic protein (GFAP) immunostaining was used to reveal reactive astrocytosis. Examination of the injured brains revealed substantial and progressive tissue loss with concomitant ventriculomegaly in the hemisphere ipsilateral to injury. The regions with the most notable progressive atrophy included the cortex, hippocampus, thalamus, and septum. Quantitative analysis demonstrated a significantly progressive loss of cortical tissue as well as shrinkage of the hippocampal pyramidal cell layer ipsilateral to injury over 1 year following injury. In addition, reactive astrocytosis in regions of atrophy and progressive bilateral death of neurons in the dentate hilus was observed for 1 year following injury. These results suggest that a chronically progressive degenerative process may be initiated by brain trauma. Thus, there is a temporally broad window within which to introduce novel therapeutic strategies designed to ameliorate the short and long-term consequences of brain trauma.

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Crossref · 10.1089/neu.1997.14.715

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  • Many biological pathways are disrupted by experimental TBI resulting in progressive neurodegeneration including atrophy, neuronal loss, and axonal degeneration which are often associated with neuroinflammation including macrophage reactivity.

    “Many biological pathways are disrupted by experimental TBI resulting in progressive neurodegeneration including atrophy, neuronal loss, and axonal degeneration which are often associated with neuroinflammation including macrophage reactivity (82–85).”
  • Excessive or chronic neuroinflammation is linked to progressive changes, including atrophy, neuronal loss, and axonal degeneration.

    “Excessive or chronic neuroinflammation is linked to progressive changes, including atrophy, neuronal loss, and axonal degeneration (84, 103–105).”

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References 35 · Cited by 440

Authors
Smith, D. H., Chen, X.-H., Pierce, J. E. S., Wolf, J. A., Trojanowski, J. Q., Graham, D. I., & McIntosh, T. K.
Affiliations
University of Pennsylvania (US)
Venue
Journal of Neurotrauma
Published
1997-10
Volume
14
Issue
10
Pages
715-727
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
OpenAlex
W2074595931
Cited by
440
References
35
Citations by year
2026: 3 · 2025: 9 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 14 · 2020: 23 · 2019: 15 · 2018: 16 · 2017: 18 · 2016: 15 · 2015: 19 · 2014: 22 · 2013: 16 · 2012: 17
FWCI
9.82
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurotrauma (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG21527)
  • National Institute of Neurological Disorders and Stroke (NS-08803, NS26818)
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, fluid percussion injury, neuronal cell death, dentate hilus, reactive astrogliosis, ventriculomegaly
MeSH terms
Animals, Atrophy, Brain Injuries, Cell Count, Cerebral Cortex, Hippocampus, Male, Neurons, Time Factors, Cell Death, Rats, Sprague-Dawley, Pyramidal Cells, Dentate Gyrus, Rats

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