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Updated: May 15, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical
Alok Kumar1, Bogdan A Stoica, Boris Sabirzhanov
1Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD, USA.
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.
Insights
Traumatic brain injury (TBI) in aging mice leads to larger lesions and increased neuroinflammation. This is linked to a shift in microglial/macrophase activation states, worsening outcomes in older animals.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Traumatic brain injury (TBI) triggers chronic microglial activation, contributing to neurodegeneration.
- Aging exacerbates TBI outcomes, with microglia/macrophages (MG/Mɸ) exhibiting distinct M1 (proinflammatory) and M2 (repair) phenotypes.
Purpose of the Study:
- To investigate the age-related changes in MG/Mɸ phenotypes and their association with lesion size and neurodegeneration after TBI.
- To determine the role of the M1/M2 balance and redox state in age-dependent TBI outcomes.
Main Methods:
- Gene expression analysis
- Immunohistochemistry
- Stereological analysis in young versus aged mice post-TBI
Main Results:
- TBI in aged mice resulted in larger lesions, altered M1/M2 balance, and increased reactive MG/Mɸ in multiple brain regions.
- Chitinase3-like 3 (Ym1) expression showed age-related, site-specific distribution.
- Aged mice exhibited increased MG/Mɸ expression of MHC II and NADPH oxidase, with reduced antioxidant enzymes, correlating with lesion size and neurodegeneration.
Conclusions:
- Age-related alterations in MG/Mɸ M1/M2 balance and NADPH oxidase-mediated redox shifts contribute to exacerbated neuroinflammation and worse outcomes after TBI in older animals.
- Targeting these age-dependent microglial responses may offer therapeutic strategies for TBI.
