Brain Advance Access originally published online on August 3, 2006
Brain 2006 129(9):2394-2403; doi:10.1093/brain/awl206
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Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice
1 Department of Neurology, Georg August University Göttingen, Germany 2 Institute of Neuropathology, Georg August University Göttingen, Germany 3 Department of Neurophysiology and Cellular Biophysics, Institute of Physiology and Pathophysiology, Georg August University Göttingen, Germany 4 Departments of Psychiatry and Experimental Neurology, Charité-Universitätsmedizin Berlin Berlin, Germany
Correspondence to: Marco Prinz, MD, Institute of Neuropathology, Georg August University, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany E-mail: mprinz{at}med.uni-goettingen.de
Previous studies have demonstrated a potential role of brain endogenous microglia and meningeal macrophages in inflammation and brain injury during bacterial meningitis. However, the contribution of previously engrafted monocytes and microglia to this process is still unknown. We therefore used genetically labelled bone marrow-derived cells from transgenic mice expressing the green fluorescent protein (GFP) under the chicken ß-actin promoter to deliver fluorescently labelled monocytes to the diseased brain. Approximately 24 hours after Streptococcus pneumoniae infection, GFP-expressing parenchymal microglia changed their morphology to an activated phenotype and upregulated major histocompatibility complex class II molecules. Bacterial meningitis increased the engraftment of GFP+ monocytes and their differentiation to microglia during the post-inflammatory period, but not during acute meningitis. Importantly, these newly recruited monocytes became an integral part of the pool of parenchymal microglia and contributed to the clearance of damaged tissue by increased lysosomal activity and close location to apoptotic cells. Thus, circulating cells entering the brain such as monocytes/macrophages might provide a potential cellular target for the treatment of the tissue damage following meningitis via peripheral cell therapy.
Key Words: GFP chimeras; meningitis; microglia turnover; S. pneumoniae
Abbreviations: BMC, bone marrow-derived cells; GFP, green fluorescent protein; MHC, major histocompatibility complex
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Received February 8, 2006. Revised June 30, 2006. Accepted July 5, 2006.
*These authors have contributed equally to this work.
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