Endotoxemia was generated in Lewis rats with intravenous injection of lipopolysaccharide (LPS, 5 mg/kg i.v.). Dura mater was removed through a cranial window to expose pial vessels on the brain surface. The microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and plasma extravasation of pial vessels was examined by fluorescent intravital microscopy (IVM) 2 h after administration of LPS, LPS and rhAPC or equivalent amount of saline (used as Control group). Plasma cytokine levels of interleukin 1 alpha (IL1-伪), tumor necrosis factor-伪 (TNF-伪), interferon 纬 (IFN-纬), Monocyte chemotactic protein-1 (MCP-1) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated after IVM.
LPS challenge significantly increased leukocyte adhesion (773 卤 190 vs. 592 卤 152 n/mm2 Control), decreased FCD (218 卤 54 vs. 418 卤 74 cm/cm2 Control) and increased proinflammatory cytokine levels (IL-1伪: 5032 卤 1502 vs. 8 卤 21 pg/ml; TNF-伪: 1823 卤 1007 vs. 168 卤 228 pg/ml; IFN-纬: 785 卤 434 vs. 0 pg/ml; GM-CSF: 54 卤 52 vs. 1 卤 3 pg/ml) compared to control animals. rhAPC treatment significantly reduced leukocyte adhesion (599 卤 111 n/mm2), increased FCD (516 卤 118 cm/cm2) and reduced IL-1伪 levels (2134 卤 937 pg/ml) in the endotoxemic rats.
APC treatment significantly improves pial microcirculation by reducing leukocyte adhesion and increasing FCD.