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

Purpose: To investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor alpha (TNF-alpha) 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 mg/kg.bw TNF-alpha 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-alpha 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-alpha administration, respectively. The expressions of CD11b/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-alpha intervention only caused responses of vascular hyperpermeability and leukocyte rolling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CD11b/CD18 and CD62L in leukocytes and E-selectin and ICAM-1 in endothelial cells induced by TNF-alpha. Conclusions: The pre- and post-applications of SAB during TNF-alpha stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling. (c) 2016 Production and hosting by Elsevier B.V. on behalf of Daping Hospital and the Research Institute of Surgery of the Third Military Medical University.