Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain.

Area of Science:

• Immunology
• Neuroscience
• Pathophysiology

Background:

• Obesity and sepsis increase cell-endothelial interactions, a marker of inflammation.
• Adiponectin, an anti-inflammatory adipokine, is crucial in managing inflammatory responses.
• The role of adiponectin deficiency in sepsis-induced brain microcirculation changes remains unclear.

Purpose of the Study:

• To investigate the impact of adiponectin deficiency on leukocyte and platelet adhesion in the cerebral microcirculation during polymicrobial sepsis.
• To determine the association between adiponectin deficiency, blood-brain barrier dysfunction, and E-selectin expression in sepsis.

Main Methods:

• Utilized adiponectin-deficient (Adipoq(-/-)) and wild-type (WT) mice subjected to cecal ligation and puncture (CLP) to induce sepsis.
• Employed intravital fluorescent video microscopy (IVM) to assess leukocyte and platelet adhesion in cerebral microcirculation.
• Measured blood-brain barrier (BBB) integrity via Evans Blue (EB) leakage and quantified E-selectin expression using dual radiolabeling.

Main Results:

• Adiponectin deficiency significantly elevated leukocyte and platelet adhesion in the cerebral microcirculation of septic mice compared to WT.
• Septic mice lacking adiponectin exhibited increased blood-brain barrier leakage and elevated E-selectin expression in brain tissue.
• Treatment with an E-selectin monoclonal antibody mitigated cell adhesion and BBB dysfunction in adiponectin-deficient septic mice.

Conclusions:

• Adiponectin deficiency exacerbates leukocyte and platelet adhesion within the brain's microvasculature during sepsis.
• E-selectin plays a critical role in mediating these adhesion events and subsequent blood-brain barrier disruption in the absence of adiponectin.
• These findings highlight adiponectin's protective role against sepsis-induced neuroinflammation and BBB damage.