Fig. 1

Pathogenesis of sepsis associated encephalopathy (SAE). Neuroinflammation and ischemic injury are considered as major causes of SAE (a), which arises from a dysregulated peripheral response to infection. The source of neuroinflammation includes both resident immune cells, such as microglia and astrocytes, and infiltration of peripheral inflammatory mediators and immune cells. In addition, inflammatory insults are responsible for the ischemic process. The inflammatory signals can reach different brain regions in both neural- and humoral-dependent manners after the initiation of septic challenge (b) and involve aberrant infiltration of blood–brain barrier (BBB), saturable transportation and specific areas without covering of BBB as well as neuro-inflammatory receptors. The abnormal immune response to infection is closely associated with the pathogenesis and progression of sepsis, according to sepsis 3.0 definition (c), and it is also a major contributor to irreversible brain damage