title: Effect of salvianolic acid B on TNF-α induced cerebral microcirculatory changes in a micro-invasive mouse model.
abstract: OBJECTIVE
  To investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor a (TNF-α) 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-α 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-α 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-α 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-α 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-α.
  
  
  CONCLUSIONS
  The pre- and post-applications of SAB during TNF-α stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.
authors.affiliation: Department of Pathophysiology, Key Laborotory for Shock and Microcirculation Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Xiang-Shun
authors.initials: XS
authors.lastname: Xu
authors.forename: Chuan-She
authors.initials: CS
authors.lastname: Wang
authors.forename: Ke-Seng
authors.initials: KS
authors.lastname: Zhao
authors.forename: Qiao-Bing
authors.initials: QB
authors.lastname: Huang
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001783:Blood Flow Velocity; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003399:Craniotomy; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects*; D011897:Random Allocation; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D053630:Depsides
chemical_list: D001572:Benzofurans; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; C076944:salvianolic acid B; D053630:Depsides