Effect of salvianolic acid B on TNF-a induced cerebral microcirculatory changes in a micro-invasive mouse model

Purpose： To investigate the effects of salvianolic acid B （SAB） on tumor necrosis factor a （TNF-a） induced alterations of cerebral microcirculation with a bone-abrading model. Methods： The influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg.bw TNF-a on cerebral venular leakage of fluorescein isothiocyanate （FITC）- albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G, The therapeutical effects of SAB on TNF-a induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg.h SAB starting at 20 min before or 20 min after TNF-a administration, respectively, The expressions of CDllb/CD18 and CD62L in leukocytes were measured with flow cytometry, Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells, Results： Compared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-a intervention only caused responses of vascular hyperpermeability and leukocyte roiling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CDII b/CDI8 and CD62L in leukocytes and E-selectin and ICAM-I in endothelial cells induced by TNF-a. Conclusions： The pre- and post-applications of SAB during TNF-a stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.