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Sepsis-Associated Encephalopathy and Blood-Brain Barrier Dysfunction

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Abstract

Sepsis is a life-threatening clinical condition caused by a dysregulated host response to infection. Sepsis-associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis, which is associated with increased morbidity and mortality. SAE clinical presentation may range from mild confusion and delirium to severe cognitive impairment and deep coma. Important mechanisms associated with SAE include excessive microglial activation, impaired endothelial barrier function, and blood-brain barrier (BBB) dysfunction. Endotoxemia and pro-inflammatory cytokines produced systemically during sepsis lead to microglial and brain endothelial cell activation, tight junction downregulation, and increased leukocyte recruitment. The resulting neuroinflammation and BBB dysfunction exacerbate SAE pathology and aggravate sepsis-induced brain dysfunction. In this mini-review, recent literature surrounding some of the mediators of BBB dysfunction during sepsis is summarized. Modulation of microglial activation, endothelial cell dysfunction, and the consequent prevention of BBB permeability represent relevant therapeutic targets that may significantly impact SAE outcomes.

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Acknowledgements

We would like to thank Dr. Kathy Griendling for her help with proofreading the manuscript. Figures were created with Biorender.com.

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M.S. Hernandes was supported by NIH HL095070, NIH HL152167, and Emory University Research Committee 00097383.

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  1. Division of Cardiology, Department of Medicine, Emory University, 101 Woodruff Circle, WMB 308, Atlanta, GA, 30322, USA

    Qingzeng Gao & Marina Sorrentino Hernandes

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QG drafted the manuscript. QG and MSH edited and revised the manuscript. QG and MSH approved the final version of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Marina Sorrentino Hernandes.

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Gao, Q., Hernandes, M.S. Sepsis-Associated Encephalopathy and Blood-Brain Barrier Dysfunction. Inflammation 44, 2143–2150 (2021). https://doi.org/10.1007/s10753-021-01501-3

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