Neurochemical effects of sepsis on the brain

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune re-sponse to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an in-flammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) func-tion; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) pro-teins and decrease BBB function. The resulting BBB permeability allows peripheral immune cells from the bloodstream to enter the brain, which then release a range of inflammatory mediators and activate glial cells. The activated microglia and astrocytes release reactive oxygen species (ROS), cytokines, chemokines, and neurochemicals, initiate mitochondrial dysfunction and neuronal damage, and exacerbate the inflammatory milieu in the brain. These changes trigger sepsis-associated encephalopathy (SAE), which has the potential to increase cognitive deterioration and susceptibility to cognitive decline later in life.

Automated summary

Sepsis is a life-threatening disorder caused by an unregulated immune response to infection. This response triggers a complex process that promotes the production of inflammatory mediators, resulting in the disruption of blood-brain barrier function and the activation of glial cells. These changes lead to sepsis-associated encephalopathy, which can contribute to cognitive deterioration and increased susceptibility to cognitive decline later in life.