Prolonged Activation of NF-κB Following Traumatic Brain Injury in Rats
Abstract
Activation of transcription factor, nuclear factor kappa B (NF-kappaB), has been shown to play a key role in inflammatory response, neuronal survival and signaling. We investigated the regional and temporal distribution of activated NF-kappaB in rats at 1 h, 2 h, 24 h, 48 h, 1 week, 2 weeks, 1 month, 2 months, 6 months, and 1 year following brain injury in rats. Early after trauma (1-2 h), activated NF-kappaB was detected in axons, and subsequently found in the cytoplasm and nucleus of neurons by 24 h and lasting up to 1 week. In addition, by 24 h posttrauma, activated NF-kappaB was detected in microglia/macrophages and astrocytes in injured cortex. Surprisingly, this activation persisted for at least 1 year following injury in the cortex, primarily at the margins of progressively enlarging ventricle. Activated NF-kappaB was also detected in endothelial cells, as early as 1 h, and persisted for up to 1 year. These results suggest that a neuronal response to brain trauma includes the activation of NF-kappaB first in the axon with subsequent translocation to the nucleus. Furthermore, these results demonstrate that remarkably prolonged activation of NF-kappaB in glia is found in the same regions undergoing persistent atrophy, suggesting NF-kappaB activation may play a role in long-term inflammatory processes following brain trauma.
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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).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [105]
TBI is a biphasic injury: after the mechanical primary injury, a secondary dystrophic state produces long-term dysfunction including elevated neuroinflammation due to blood-brain barrier disruption, increased oxidative stress, and persistent changes in the microglial population.
“TBI is a biphasic injury: after the mechanical primary injury, a secondary dystrophic state produces long-term dysfunction in the brain that includes elevated neuroinflammation as a result of blood-brain barrier disruption, increased oxidative stress, and persistent changes in the microglial population [100–106].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [104]
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- Authors
- NONAKA, M., CHEN, X.-H., PIERCE, J. E. S., LEONI, M. J., McINTOSH, T. K., WOLF, J. A., & SMITH, D. H.
- Affiliations
- University of Pennsylvania Health System (US)
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 1999-11
- Volume
- 16
- Issue
- 11
- Pages
- 1023-1034
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- OpenAlex
- W2005401338
- Cited by
- 176
- References
- 61
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 3 · 2018: 10 · 2017: 8 · 2016: 5 · 2015: 8 · 2014: 10 · 2013: 5 · 2012: 9
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG12527, R01AG012527)
- National Institute of Neurological Disorders and Stroke (R01NS038104, NS-08803, NS38104)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- NF-κB activation, traumatic brain injury, neuroinflammation, microglia/macrophages, astrocytes, endothelial cells, ventriculomegaly, cortical atrophy
- MeSH terms
- Animals, Brain Injuries, Endothelium, Male, Neuroglia, Neurons, Time Factors, NF-kappa B, Rats, Sprague-Dawley, Mice, Rats
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