Fig. 4
From: Post-sepsis syndrome – an evolving entity that afflicts survivors of sepsis
Mechanisms of cognitive decline after sepsis. The neurocognitive effects of sepsis are caused by a combination of cerebral ischemia, neuronal dysfunction, and neuroinflammation. These three contributory pathways are associated with persistently elevated levels of HMGB1, a cytokine secreted by immune cells (e.g. monocytes, macrophages, and dendritic cells) during the late stages of sepsis. Systemic endothelial dysfunction and variations in blood pressure lead to poor blood flow to the brain and contribute to cerebral ischemia. Cholinergic dysfunction is related to increased acetylcholinesterase activity and a decrease in receptor density in the hippocampus; this pathophysiology is a major contributor to impaired neurotransmission. Activation of microglia and astroglia produce increased inflammatory mediators (tumor necrosis factor, interleukin-6, and interleukin-12) and is associated with compromised blood-brain barrier integrity that allows for the passage of neurotoxic factors (cytokines, reactive oxygen species, and glutamate) and sustained neuroinflammation