Fig. 1

The transition from healthy to sepsis-associated brain dysfunction. In healthy conditions, resting microglia and astrocytes are predominant and are important to maintain several different brain functions. In addition, microglia could be primed, and in this context produces exaggerated levels of inflammatory cytokines in response to a stimulus. Systemic inflammation could activate both resting and primed microglia. Activated microglia could simultaneously exhibit M1 and M2 phenotypes. Despite the fact that classically M1 phenotype is associated with brain damage, during some conditions, the M2 phenotype could also be detrimental to brain function. In addition, astrocytes are also activated, lose the ability to maintain low the extracellular levels of glutamate, to maintain the integrity of the blood-brain barrier, and secrete chemokines. All these modifications are powerful stimuli to the chemotaxis of blood-borne leukocytes that also contribute to sepsis-associated brain dysfunction