Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states

Kumar, Alok; Stoica, Bogdan A.; Sabirzhanov, Boris; Burns, Mark P.; Faden, Alan I.; Loane, David J.

doi:10.1016/j.neurobiolaging.2012.11.013

Cited by 244Traumatic Brain Injury and Neurovascular DisturbancesNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury Research

Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states

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Kumar, Alok, Stoica, Bogdan A., Sabirzhanov, Boris, Burns, Mark P., Faden, Alan I., Loane, David J.·2013·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2012.11.013PMC PMC3572914

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Abstract

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.

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The mode of microglial activation following TBI is somewhat age-dependent and may be less neuroprotective and more toxic in older animals.
“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]
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.
“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]

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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.
ORCID: Kumar, Alok
Stoica, Bogdan A.
Burns, Mark P.
Faden, Alan I.
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)
DOI: 10.1016/j.neurobiolaging.2012.11.013
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Epidemiology › 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

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Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states

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