Altered Neuroinflammation and behavior after traumatic brain injury in a mouse model of Alzheimer’s disease
Open accessAbstract
Traumatic brain injury (TBI) has acute and chronic sequelae, including an increased risk for the development of Alzheimer's disease (AD). TBI-associated neuroinflammation is characterized by activation of brain-resident microglia and infiltration of monocytes; however, recent studies have implicated beta-amyloid as a major manipulator of the inflammatory response. To examine neuroinflammation after TBI and development of AD-like features, these studies examined the effects of TBI in the presence and absence of beta-amyloid. The R1.40 mouse model of cerebral amyloidosis was used, with a focus on time points well before robust AD pathologies. Unexpectedly, in R1.40 mice, the acute neuroinflammatory response to TBI was strikingly muted, with reduced numbers of CNS myeloid cells acquiring a macrophage phenotype and decreased expression of inflammatory cytokines. At chronic time points, macrophage activation substantially declined in non-Tg TBI mice; however, it was relatively unchanged in R1.40 TBI mice. The persistent inflammatory response coincided with significant tissue loss between 3 and 120 days post-injury in R1.40 TBI mice, which was not observed in non-Tg TBI mice. Surprisingly, inflammatory cytokine expression was enhanced in R1.40 mice compared with non-Tg mice, regardless of injury group. Although R1.40 TBI mice demonstrated task-specific deficits in cognition, overall functional recovery was similar to non-Tg TBI mice. These findings suggest that accumulating beta-amyloid leads to an altered post-injury macrophage response at acute and chronic time points. Together, these studies emphasize the role of post-injury neuroinflammation in regulating long-term sequelae after TBI and also support recent studies implicating beta-amyloid as an immunomodulator.
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Several experimental studies have failed to show that TBI induces or worsens AD-related pathology, with some even reporting a reduction in post-injury Aβ accumulation in transgenic mice.
“Finally, several experimental studies have failed to show that TBI induces or worsens AD-related pathology (38, 39) with some even reporting a reduction in post-injury Aβ accumulation in transgenic mice (40, 41).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [38]
The glial response to TBI is altered in the presence of Aβ and correlates with altered functional recovery.
“demonstrate that the glial response to TBI is altered in the presence of Aβ and correlates with altered functional recovery (38).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [38]
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Mast cell-mediated immune regulation in health and disease
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Brain Injury–Mediated Neuroinflammatory Response and Alzheimer’s Disease
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Inflammasome activation in traumatic brain injury and Alzheimer's disease
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Sleep Disruption Exacerbates and Prolongs the Inflammatory Response to Traumatic Brain Injury
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Monocytes in the Peripheral Clearance of Amyloid-β and Alzheimer’s Disease
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Glycerophospholipid dysregulation after traumatic brain injury
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Self-citationMilitary‐related risk factors for dementia
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Self-citationmiR-146a Mimics Ameliorates Traumatic Brain Injury Involving JNK and NF-κB Signaling Pathway
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Possibilities and Prospects of the Behavioral Test “Morris Water Maze”
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Self-citationTraumatic Brain Injury Alters the Metabolism and Facilitates Alzheimer’s Disease in a Murine Model
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Self-citationGenetic diversity drives extreme responses to traumatic brain injury and post-traumatic epilepsy
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Self-citationAdolescent mice exposed to TBI developed PD-like pathology in middle age
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- Authors
- Kokiko-Cochran, O., Ransohoff, L., Veenstra, M., Lee, S., Saber, M., Sikora, M., Teknipp, R., Xu, G., Bemiller, S., Wilson, G., Crish, S., Bhaskar, K., Lee, Y.-S., Ransohoff, R. M., & Lamb, B. T.
- Affiliations
- Cleveland Clinic
- Cleveland Clinic (US)
- Northeast Ohio Medical University (US)
- University of New Mexico (US)
- Biogen (United States) (US)
- Corresponding author
- Lamb, Bruce T.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2016-04
- Volume
- 33
- Issue
- 7
- Pages
- 625-640
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC4971425
- OpenAlex
- W2177343272
- Cited by
- 49
- References
- 82
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 2 · 2020: 2 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 3
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- National Eye Institute (EY022358, R01EY022358)
- National Institute of Neurological Disorders and Stroke (RF1NS083704, R01NS069765)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- traumatic brain injury, Alzheimer's disease, neuroinflammation, amyloid-beta, cerebral amyloidosis, microglia, macrophage activation, myeloid cells, inflammatory cytokines, cognitive impairment, tissue loss, immunomodulation
- MeSH terms
- Brain Injuries, Traumatic, Alzheimer Disease, Animals, Behavior, Animal, Brain, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunohistochemistry, Inflammation, Mice, Inbred C57BL, Mice, Transgenic, Blotting, Western, Amyloid beta-Peptides, Mice
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