Clinical, Molecular, and Exosomal Mechanisms of Cardiac and Brain Dysfunction in Sepsis

Abstract

Sepsis is a complex disease resulting from a dysregulated inflammatory response to an infection. Initiation of sepsis occurs from a localized infection that disseminates to the bloodstream placing all organ systems at risk. Septic shock is classically observed to manifest itself as systemic hypotension with hyporesponsiveness to vasopressor agents. Myocardial dysfunction occurs resulting in an inability to perfuse major organ systems throughout the body. Most importantly, the brain is hypoperfused creating an ischemic and inflammatory state resulting in the clinical observation of acute mental status changes and cognitive dysfunction commonly known as sepsis-associated encephalopathy. This short review describes the inflammatory molecular mechanisms of myocardial dysfunction, discusses the evidence of the dual roles of the microglia resulting in blood-brain barrier disruption, and suggests that septic-derived exosomes, endosome-derived lipid bilayer spheroids released from living cells, influence cardiac and neurological cellular function.

Role of microglia in sepsis-associated encephalopathy pathogenesis: an update

“…Under hypoxic conditions, microglia in the brain tend to show increased expression of the activation markers, Iba1 and NO (104). Septic shock causes neuroinflammation by activating microglia because of reduced blood flow to the brain, thus impairing brain function and causing SAE (105). Microglia can worsen brain tissue damage in SAE by detecting changes in the brain microenvironment and contributing to processes including oxidative stress, vascular endothelial injury, and mitochondrial damage that promote cerebral ischemic-hypoxic injury.…”