The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation.

Autor: Sawyer AJ; Department of Pathology, Yale School of Medicine, 310 Cedar Street LH 108, New Haven, CT 06520-8023, USA., Tian W; Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China., Saucier-Sawyer JK; Department of Biomedical Engineering, Yale University, New Haven, CT, USA., Rizk PJ; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA., Saltzman WM; Department of Biomedical Engineering, Yale University, New Haven, CT, USA., Bellamkonda RV; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA., Kyriakides TR; Department of Pathology, Yale School of Medicine, 310 Cedar Street LH 108, New Haven, CT 06520-8023, USA; Department of Biomedical Engineering, Yale University, New Haven, CT, USA. Electronic address: themis.kyriakides@yale.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2014 Aug; Vol. 35 (25), pp. 6698-706. Date of Electronic Publication: 2014 May 29.
DOI: 10.1016/j.biomaterials.2014.05.008
Abstrakt: Intracranial implants elicit neurodegeneration via the foreign body response (FBR) that includes BBB leakage, macrophage/microglia accumulation, and reactive astrogliosis, in addition to neuronal degradation that limit their useful lifespan. Previously, monocyte chemoattractant protein 1 (MCP-1, also CCL2), which plays an important role in monocyte recruitment and propagation of inflammation, was shown to be critical for various aspects of the FBR in a tissue-specific manner. However, participation of MCP-1 in the brain FBR has not been evaluated. Here we examined the FBR to intracortical silicon implants in MCP-1 KO mice at 1, 2, and 8 weeks after implantation. MCP-1 KO mice had a diminished FBR compared to WT mice, characterized by reductions in BBB leakage, macrophage/microglia accumulation, and astrogliosis, and an increased neuronal density. Moreover, pharmacological inhibition of MCP-1 in implant-bearing WT mice maintained the increased neuronal density. To elucidate the relative contribution of microglia and macrophages, bone marrow chimeras were generated between MCP-1 KO and WT mice. Increased neuronal density was observed only in MCP-1 knockout mice transplanted with MCP-1 knockout marrow, which indicates that resident cells in the brain are major contributors. We hypothesized that these improvements are the result of a phenotypic switch of the macrophages/microglia polarization state, which we confirmed using PCR for common activation markers. Our observations suggest that MCP-1 influences neuronal loss, which is integral to the progression of neurological disorders like Alzheimer's and Parkinson disease, via BBB leakage and macrophage polarization.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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