THERAPEUTIC IMPLICATIONS OF MICROGLIA ACTIVATION BY LIPOPOLYSACCHARIDE AND REACTIVE OXYGEN SPECIES GENERATION IN SEPTIC SHOCK AND CENTRAL-NERVOUS-SYSTEM PATHOLOGIES - A REVIEW

The pathophysiology of organ system failure in sepsis, in particular t he effects of septic shock on the central nervous system, are still in completely understood. Lipopolysaccharide(LPS) from Gram-negative bact eria affects the permeability of the blood-brain barrier and causes th e activation of brain microglia. A growing body of research supports i nvolvement of activated brain microglia in brain pathologies caused by infectious diseases, trauma, tumors, ischemia, Alzheimer's disease, P arkinson's disease, Down's syndrome, multiple sclerosis and AIDS. Thos e seminal studies that have contributed to the characterization of the in vivo and in vitro effects of LPS on microglia function, mediator g eneration and receptor expression are presented within a historical pe rspective. In particular, all those in vitro studies on O-2(-), H2O2 a nd NO . generation by either unprimed or primed microglia have been ex tensively reviewed. The apparent controversial effect of LPS on microg lia O-2(-) is discussed. Because treatment modalities for septic shock have not significantly affected the current high mortality, alternati ve strategies with antioxidants are currently being investigated. Redu ction of microglia O-2(-) generation is proposed as a possible complem entary strategy to antioxidative therapy for septic shock and CNS path ologies that involve activated microglia.