Sepsis-associated delirium: the pro and con of C5a blockade

The intimate mechanisms of sepsis-induced delirium are unknown. Among the potential contributing factors, the breakdown of the blood-brain barrier is considered a key determinant of brain dysfunction. The complement activation is paramount to an appropriate activation of the central nervous system during stress. C3a and C5a have been extensively studied and may be involved in sepsis-induced delirium. Here we discuss the pro and con for inhibiting C5a to attenuate brain damage during sepsis. In particular, we discuss the hypothesis that C5a increased blood-brain barrier permeability amy ease the brain to mount an appropriate response to sepsis. Thus, blockade of C5a may be detrimental, resulting in an attenuated response of the stress system.