The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states
Open accessAbstract
Traumatic brain injury (TBI) causes chronic microglial activation that contributes to subsequent neurodegeneration, with clinical outcomes declining as a function of aging. Microglia/macrophages (MG/Mɸ) have multiple phenotypes, including a classically activated, proinflammatory (M1) state that might contribute to neurotoxicity, and an alternatively activated (M2) state that might promote repair. In this study we used gene expression, immunohistochemical, and stereological analyses to show that TBI in aged versus young mice caused larger lesions associated with an M1/M2 balance switch and increased numbers of reactive (bushy and hypertrophic) MG/Mɸ in the cortex, hippocampus, and thalamus. Chitinase3-like 3 (Ym1), an M2 phenotype marker, displayed heterogeneous expression after TBI with amoeboid-like Ym1-positive MG/Mɸ at the contusion site and ramified Ym1-positive MG/Mɸ at distant sites; this distribution was age-related. Aged-injured mice also showed increased MG/Mɸ expression of major histocompatibility complex II and NADPH oxidase, and reduced antioxidant enzyme expression which was associated with lesion size and neurodegeneration. Thus, altered relative M1/M2 activation and an nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase)-mediated shift in redox state might contribute to worse outcomes observed in older TBI animals by creating a more proinflammatory M1 MG/Mɸ activation state.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The mode of activation following TBI is somewhat age-dependent and may be less neuroprotective and more toxic in older animals [109].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [109]
In the citing paper
“Elderly individuals are at greater risk to suffer significant cognitive impairment and early morbidity following TBI, potentially due to an already present dysfunction in the microglial compartment [109,122,123].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [109]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
National Center for Injury Prevention and Control (U.S.). Division of Injury Response., Faul, M., Wald, M. M., Wu, L., & Coronado, V. G. (2010) · doi:10.15620/cdc.5571 · Cited by 3,494
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130
Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism
Block, M. L., & Hong, J.-S. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.004 · Cited by 1,557
Microglial Activation and Chronic Neurodegeneration
Lull, M. E., & Block, M. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.014 · Cited by 1,047 · cited 4×
“…species (ROS) by phagocytic cells including MG. NADPH oxidase has been implicated as a common and essential mechanism of MGmediated neurotoxicity (Lull and Block, 2010), and NADPH oxidase plays a critical role in the modulation of MG/MΦ activation phenotype and subsequent inflammatory…”
BackgroundInfluentialHeterogeneity of Microglial Activation in the Innate Immune Response in the Brain
Colton, C. A. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9164-4 · Cited by 916
Godbout, J. P., Chen, J., Abraham, J., Richwine, A. F., Berg, B. M., Kelley, K. W., & Johnson, R. W. (2005) · The FASEB Journal · doi:10.1096/fj.05-3776fje · Cited by 813
Neuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention
Kumar, A., & Loane, D. J. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.06.008 · Cited by 710
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–244 of 244
Tchantchou, F., Hsia, R., Puché, A. C., & Fiskum, G. M. (2023) · Journal of Central Nervous System Disease · doi:10.1177/11795735231160025 · Cited by 6
Aging Effects on Lipid Metabolism in Response to Traumatic Brain Injury
Fernandez, R. F., Weglarczyk, P., Zokaei, S., Huguenin, S. M., Scafidi, J., Ellis, J. M., & Scafidi, S. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70227 · Cited by 4
Jiang, F., Chen, Z., Hu, J., & Liu, Q. (2022) · International Journal of General Medicine · doi:10.2147/ijgm.s366170 · Cited by 4
Effects of age on retinal macrophage responses to acute elevation of intraocular pressure
Kezic, J. M., Chrysostomou, V., McMenamin, P. G., & Crowston, J. G. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.107995 · Cited by 3
Kwon, H., Kim, S., Kim, J., Kim, Y., & Kim, W. Y. (2024) · Internal and Emergency Medicine · doi:10.1007/s11739-024-03662-z · Cited by 3
Michalettos, G., Clausen, F., Rostami, E., & Marklund, N. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00472 · Cited by 3
Nakajima, S., Matsuyama, T., Okada, N., Kandori, K., Okada, A., Okada, Y., Kitamura, T., & Ohta, B. (2023) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2023.01.027 · Cited by 3
Chodobski, A., Zink, B. J., & Szmydynger‐Chodobska, J. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8690-9_1 · Cited by 3
McLeod, R. E., Kale, K. M., Weglinski, C., Masoud, A. M., Akbar, N., Probert, F., Anthony, D. C., & Zainal, J. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.07.027 · Cited by 2
Correa, F. G., Melendes, E. J., Yin, Y., Orbach, G., Warren, K., Nosek, N., Tillman-Schwartz, A., Leahy, C., Kheir, E. A., Lu, J., et al. (2025) · Journal of Neurotrauma · doi:10.1177/08977151251365669 · Cited by 2
Neuroglia in traumatic brain injury: Pathophysiology and therapeutic targeting
Suk, K. (2026) · Brain Network Disorders · doi:10.1016/j.bnd.2026.03.002 · Cited by 2
Cognition and Behavior in the Aging Brain Following TBI: Surveying the Preclinical Evidence
Race, N. S., Moschonas, E. H., Kline, A. E., & Bondi, C. O. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-69832-3_11 · Cited by 2
Poddar, J., Rangasamy, S. B., & Pahan, K. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105742 · Cited by 1
Barrett, J. P., Henry, R. J., Vaida, M. L., Shirey, K. A., Vogel, S. N., Faden, A. I., & Stoica, B. A. (2026) · Journal of Neurotrauma · doi:10.1177/08977151261434894 · Cited by 1
Self-citationAdvanced age is not a barrier to chronic intracortical single-unit recording in rat cortex
Nolta, N. F., Christensen, M. B., & Tresco, P. A. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1389556 · Cited by 1
Lindblad, C., & Thelin, E. P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11528-4 · Cited by 1
Fenn, A. M., Norden, D. M., & Godbout, J. P. (2015) · Wiley eBooks · doi:10.1002/9781118732748.ch6 · Cited by 1
Animal Models in Translational Research
Bolker, J. A. (2019) · Wiley eBooks · doi:10.1002/9780470015902.a0028711 · Cited by 1
Drima, E. P., & Vrabie, C. D. (2020) · Preprints.org · doi:10.20944/preprints202012.0314.v1 · Cited by 1
Przebieg procesu zapalnego w narządach immunologicznie uprzywilejowanych
MADEJ, J. A., Madej, J. P., & Kandefer-Gola, M. (2013) · Medycyna Weterynaryjna
Ageing and the Immune Response in the CNS
Raj, D. D. A., Eggen, B. J. L., & Boddeke, H. W. G. M. (2014) · Wiley eBooks · doi:10.1002/9781118406557.ch4
Therapeutic Targeting of Neuronal Mitochondria in Brain Injury
Yonutas, H. M., Hall, E. D., & Sullivan, P. G. (2015) · Wiley eBooks · doi:10.1002/9781119017127.ch17
Elucidating and Pharmacologically Targeting Secondary Injury Cascades following Neural Injury
Lucke-Wold, B. P. (2016) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.6120
Microglia: Features of Polarization and Aging
Harry, G. J., & McPherson, C. A. (2016) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-3-319-33486-8_3
Nolta, N. F. (2018) · J. Willard Marriott Library · doi:10.26053/0h-sqbe-9pg0
The Regenerative Response of Endogenous Neural Stem/Progenitor Cells to Traumatic Brain Injury
Sullivan, G. M. (2014) · Defense Technical Information Center (DTIC) · doi:10.21236/ad1012867
Aging exacerbates myelin disruption and axon injury following demyelination
Michaels, N. J. (2019) · doi:10.11575/prism/36466
Interleukin 33 Initiates CNS Inflammation Following Traumatic Injury
Gadani, S. P. (2016) · doi:10.18130/v3xw3s
Elucidating Mechanisms of Neurobehavioral Dysfunction in a Rodent Model of Traumatic Brain Injury
Logsdon, A. F. (2016) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.6106
Jadhav, V. (2021) · IUScholarWorks (Indiana University) · doi:10.7912/c2/2086
Popovich, P. G. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.727777924.793557639
Aging, the immune response, and traumatic brain injury
Sun, M., & Shultz, S. R. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823036-7.00035-9
Microglia in traumatic brain injury
Raghupathi, R., Lengel, D., & Huh, J. W. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823036-7.00011-6
Failla, M. D. (2014) · D-Scholarship@Pitt (University of Pittsburgh)
Lassarén, P., Lindblad, C., Frostell, A., Carpenter, K. L. H., Guilfoyle, M. R., Hutchinson, P. J. A., Helmy, A. E., & Thelin, E. P. (2021) · Figshare · doi:10.6084/m9.figshare.16681661
Lassarén, P., Lindblad, C., Frostell, A., Carpenter, K. L. H., Guilfoyle, M. R., Hutchinson, P. J. A., Helmy, A. E., & Thelin, E. P. (2021) · Figshare · doi:10.6084/m9.figshare.16681679
Lassarén, P., Lindblad, C., Frostell, A., Carpenter, K. L. H., Guilfoyle, M. R., Hutchinson, P. J. A., Helmy, A. E., & Thelin, E. P. (2021) · Figshare · doi:10.6084/m9.figshare.16681658
Lassarén, P., Lindblad, C., Frostell, A., Carpenter, K. L. H., Guilfoyle, M. R., Hutchinson, P. J. A., Helmy, A. E., & Thelin, E. P. (2021) · Figshare · doi:10.6084/m9.figshare.16681664
Contribution of astrocytes in brain vulnerability after juvenile mild traumatic brain injury
Clément, T. (2020) · theses.fr (ABES) · doi:10.70675/2892171fzc838z4d9azbf65zf208dafdf173
Michalettos, G., Ruscher, K., & Marklund, N. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115761
You, W., Wu, Y., Fang, Y., Shen, S., & Cai, W. (2026) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2026.112038
Chen, L., Li, Y., Han, L., & Lu, S. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1876873
Mayilsamy, K., Patel, P. B., Green, R. J., Bikkasani, S., Tosi, K., Majumdar, S., Prajapati, S. K., Markoutsa, E., Wolf, T., Guergues, J., et al. (2026) · Molecular Therapy · doi:10.64898/2026.09.04.748639
Metadata
- Authors
- Kumar, A., Stoica, B. A., Sabirzhanov, B., Burns, M. P., Faden, A. I., & Loane, D. J.
- Affiliations
- University of Maryland, Baltimore (US)
- Georgetown University Medical Center (US)
- Corresponding author
- Loane, David J.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 34
- Issue
- 5
- Pages
- 1397-1411
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC3572914
- OpenAlex
- W2043020388
- Cited by
- 244
- References
- 69
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 13 · 2023: 10 · 2022: 14 · 2021: 16 · 2020: 21 · 2019: 15 · 2018: 21 · 2017: 24 · 2016: 33 · 2015: 27 · 2014: 25 · 2013: 10
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Capital Area Rehabilitation Research Network (R24HD050845)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, aging, microglial activation, macrophages, macrophage polarization, Ym1, NADPH oxidase, MHC class II, antioxidant enzymes, neurodegeneration, lesion size, reactive microglia, redox state, proinflammation
- MeSH terms
- Aging, Animals, Brain, Brain Injuries, Cells, Cultured, Chronic Disease, Macrophage Activation, Macrophages, Male, Mice, Inbred C57BL, Microglia, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
