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Obesity Exacerbates Sepsis‐Induced Inflammation and Microvascular Dysfunction in Mouse Brain
Author(s) -
VACHHARAJANI VIDULA,
RUSSELL JANICE M.,
SCOTT KEITH L.,
CONRAD STEVEN,
STOKES KAREN Y.,
TALLAM LAKSHMI,
HALL JOHN,
GRANGER D. NEIL
Publication year - 2005
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680590904982
Subject(s) - sepsis , inflammation , medicine , proinflammatory cytokine , p selectin , perforation , platelet , endocrinology , intravital microscopy , immunology , platelet activation , microcirculation , materials science , punching , metallurgy
Objective: Obese patients with sepsis have higher morbidity and mortality than lean counterparts, but the mechanisms involved are unknown. The authors examined the inflammatory and thrombogenic responses of the cerebral microvasculature to sepsis induced by cecal ligation and perforation in obese and lean wild‐type mice. Methods: Leukocyte and platelet adhesion in cerebral microvasculature and behavioral responses were measured in wild‐type and obese mice 4 h postperforation. P‐selectin expression in different vascular beds was assessed 6 h postperforation. The effects of immunoblockade of P‐selectin, ICAM‐1, and CD18 on leukocyte and platelet recruitment were evaluated in obese septic animals. Results: Cerebral venules of obese and wild‐type mice assumed a proinflammatory and prothrombogenic phenotype 4 h post‐perforation, with greatly exaggerated responses in obese mice compared to the lean counterparts. These enhanced responses were attenuated by blocking P‐selectin, CD18, or ICAM‐1. Obese mice also exhibited a more profound behavioral deficit after sepsis, which appears to be unrelated to the recruitment of leukocytes and platelets. Cecal ligation and perforation‐induced P‐selectin expression was greater in obese mice compared with lean counterparts. Conclusions: These findings suggest that the increased morbidity to sepsis in obesity may result from exaggerated microvascular inflammatory and thrombogenic responses that include the activation of endothelial cells with subsequent expression of adhesion molecules, such as P‐selectin.