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

NEUROBIOLOGY OF AGING

卷:34

Article

Kumar, Alok^1,2  Stoica, Bogdan A.^1,2  Sabirzhanov, Boris^1,2  Burns, Mark P.³  Faden, Alan I.^1,2  Loane, David J.^1,2 

[1] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA

[2] Univ Maryland, Sch Med, Ctr Shock Trauma & Anesthesiol Res STAR, Baltimore, MD 21201 USA

[3] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA

关键词: Microglia/macrophage;    Alternative activation;    Traumatic brain injury;    Aging;    NADPH oxidase;    Neurodegeneration;    Ym1;   

DOI  :  10.1016/j.neurobiolaging.2012.11.013

来源: Elsevier

【 摘 要 】

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/M phi) 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/M phi 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/M phi at the contusion site and ramified Ym1-positive MG/M phi at distant sites; this distribution was age-related. Aged-injured mice also showed increased MG/M phi 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/M phi activation state. (C) 2013 Elsevier Inc. All rights reserved.

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