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Activation of cerebral endothelium is required for mononuclear cell recruitment in a novel in vitro model of brain inflammation

, : Activation of cerebral endothelium is required for mononuclear cell recruitment in a novel in vitro model of brain inflammation. Neuroscience 137(4): 1211-1219

Brain inflammation is a common event in the pathogenesis of several neurological diseases. It is unknown whether leukocyte/endothelium interactions are sufficient to promote homing of blood-borne cells into the brain compartment. The role of mononuclear cells and endothelium was analyzed in a new experimental model, the isolated guinea-pig brain maintained in vitro by arterial perfusion. This preparation allows one to investigate early steps of brain inflammation that are impracticable in vivo. We demonstrate by confocal microscopy analysis that in vitro co-perfusion of pro-inflammatory agents and pre-activated fluorescent mononuclear cells induced endothelial expression of selectins and intracellular adhesion molecule-1 in correspondence of arrested mononuclear cells, and correlates with a moderate increase in bloodbrain barrier permeability. Separate perfusion of pro-inflammatory agents and mononuclear cells induced neither mononuclear cell adhesion nor adhesion molecule expression. We demonstrate that co-activation of mononuclear cells and cerebral endothelium is an essential requirement for cell arrest and adhesion in the early stages of experimental cerebral inflammation. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.


PMID: 16359809

DOI: 10.1016/j.neuroscience.2005.10.041

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