title: Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain.
abstract: Obesity increases circulating cell-endothelial cell interactions; an early marker of inflammation in laboratory model of sepsis, but little is known about the effect of different adipokines. Adiponectin is an anti-inflammatory adipokine secreted by adipocytes. Adiponectin deficiency is implicated in exaggerated proinflammatory phenotype in both obesity and sepsis via increased proinflammatory cytokine expression. However the effect of adiponectin deficiency on circulating cell-endothelial cell interactions in polymicrobial sepsis is unknown. Furthermore although brain dysfunction in septic patients is a known predictor of death, the pathophysiology involved is unknown. In the current study, we examined the effects of adiponectin deficiency on leukocyte (LA) and platelet adhesion (PA) in cerebral microcirculation of septic mice. Adiponectin deficient (Adipoq(-/-): Adko) and background strain C57Bl/6 (wild type (WT)) mice were used. Sepsis was induced using cecal ligation and puncture (CLP). We studied LA and PA in the cerebral microcirculation using intravital fluorescent video microscopy (IVM), blood brain barrier (BBB) dysfunction using Evans Blue (EB) leakage method and E-selectin expression using dual radiolabeling technique in different WT and Adko mice with CLP. Adiponectin deficiency significantly exaggerated LA (WT-CLP:201 ± 17; Adko-CLP: ± 53 cells/mm(2); P < 0.05) and PA (WT-CLP:125 ± 17; Adko-CLP:188 ± 20 cells/mm(2); P < 0.05) in cerebral microcirculation, EB leakage (WT-CLP:10 ± 3.7; Adko-CLP:24 ± 4.3 ng/g × µl plasma; P < 0.05) and E-selectin expression (WT-CLP:0.06 ± 0.11; Adko-CLP:0.44 ± 0.053 ng/g; P < 0.05) in the brain tissue of the mice with CLP. Furthermore, E-selectin monoclonal antibody (mAb) treatment attenuated cell adhesion and BBB dysfunction of Adko-CLP mice. Adiponectin deficiency is associated with exaggerated leukocyte and PA in cerebral microcirculation of mice with CLP via modulation of E-selectin expression.
authors: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. vvachhar@wfubmc.edu
authors: Vidula
authors: V
authors: Vachharajani
authors: Christie
authors: C
authors: Cunningham
authors: Barbara
authors: B
authors: Yoza
authors: John
authors: J
authors: Carson
authors: Tushar J
authors: TJ
authors: Vachharajani
authors: Charles
authors: C
authors: McCall
mesh_terms: D052242:Adiponectin / Q000172:deficiency* / Q000276:immunology; D000818:Animals; D001812:Blood-Brain Barrier; D002448:Cell Adhesion / Q000276:immunology; D002560:Cerebrovascular Circulation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D005453:Fluorescence; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D008853:Microscopy / Q000379:methods; D009765:Obesity / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D010973:Platelet Adhesiveness / Q000276:immunology; D016719:Radioimmunodetection; D018805:Sepsis / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D014741:Video Recording
chemical_list: D052242:Adiponectin; D016207:Cytokines; D019040:E-Selectin