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

Abstract 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 blood–brain 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.