Librizzi L, Mazzetti S, Pastori C, Frigerio S, Salmaggi A, Buccellati C, Di Gennaro A, Folco G, Vitellaro-Zuccarello L, de Curtis M
Dipartimento di Neurofisiologia Sperimentale, Istituto Nazionale Neurologico, Via Celoria, 11 20133 Milano, Italy.
Neuroscience. 2006;137(4):1211-9. doi: 10.1016/j.neuroscience.2005.10.041. Epub 2005 Dec 15.
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.
脑炎症是几种神经疾病发病机制中的常见事件。目前尚不清楚白细胞/内皮细胞相互作用是否足以促进血源性细胞归巢至脑区室。在一个新的实验模型中分析了单核细胞和内皮细胞的作用，该模型是通过动脉灌注体外维持的分离豚鼠脑。这种制备方法使人们能够研究在体内无法进行的脑炎症早期步骤。我们通过共聚焦显微镜分析证明，在体外将促炎剂与预激活的荧光单核细胞共同灌注，可诱导选择素和细胞间黏附分子-1在内皮细胞中的表达，且这些表达与停滞的单核细胞相对应，并且与血脑屏障通透性的适度增加相关。单独灌注促炎剂和单核细胞既不会诱导单核细胞黏附，也不会诱导黏附分子表达。我们证明，单核细胞和脑内皮细胞的共同激活是实验性脑炎症早期细胞停滞和黏附的必要条件。
