EFFECTS OF MONOCYTE CHEMOATTRACTANT PROTEIN 1 ON BLOOD-BORNE CELL RECRUITMENT AFTER TRANSIENT FOCAL CEREBRAL ISCHEMIA IN MICE

Monocyte chemoattractant protein 1 (MCP-1) plays an important role in inflammatory reactions following cerebral ischemia. It is known that MCP-1 overexpression leads to increased infarct volume and elevated hematogenous cell recruitment, while MCP-1-deficient mice develop smaller infarcts. It was supposed that MCP-1 dependent macrophage recruitment might be the underlying mechanism of ischemic brain damage but a precise distinction of local microglia and invading macrophages was not performed. In this study we investigated the differential role of MCP-1 on inflammatory cells in MCP-1-deficient mice, using green fluorescent protein (GFP) transgenic bone marrow chimeras. After 30-min of focal cerebral ischemia microglia was rapidly activated and was not different between MCP-1-deficient mice and wild type controls. Activated microglia outnumbered GFP-positive macrophages over the study period. Furthermore, macrophage infiltration was significantly reduced at day 7 in MCP-1-deficient animals (31.2 +/- 20.1 cells/mm(2)) compared to MCP-1 wild type mice (131.5 +/- 66.7 cells/mm(2), P<0.001). Neutrophils were also significantly reduced in MCP-1-deficient mice (62% on day 4% and 87% on day 7; P<0.001). This is the first investigation in cerebral ischemia showing that MCP-1 is necessary for recruiting blood-borne cells to the injury site whereas it does not affect the microglia activation and migration. However, the remarkable predominance of activated microglia and the additional attenuation of invading macrophages suggest that different mechanisms than macrophage recruitment are responsible for the MCP-1-mediated neuroprotective effects after experimental stroke. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.