Pathophysiology of sepsis associated encephalopathy. Altered brain signalling during sepsis occurring as a result of centrally and peripherally acting cytokines results in production of various inflammatory cytokines that cause activation of various behavioral, neuroendocrine, and neurovegetative centers which can cause altered behaviour. In addition these cytokines cause microglial activation thus perpetuating the production of inflammatory cytokines and reactive oxygen species. Peripherally produced LPS, cytokines, and NO cause further damage to the BBB thereby causing a vicious cycle of brain damage. The excessive production of LPS and cytokines causes increased production of NO and other ROS thereby causing mitochondrial dysfunction and apoptosis. Altered amino acid balance because of excessive muscle proteolysis is responsible for production of false neurotransmitters which can also contribute to the pathogenesis of SAE. Disturbed cerebral autoregulation and direct cerebral localization may play a minor role. NO: nitrous oxide, ROS: reactive oxygen species, LPS: lipopolysaccharide, TNF-α: tumor necrosis factor-α, AAA: aromatic amino acids, and BBB: blood brain barrier.
