The role of glial activation on the pathogenesis of septic encephalopathy

Sepsis often leads to a multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Symptoms of gram-negative bacterial sepsis can be reproduced experimentally by treatment of animals with LPS, a component of the cell wall of Gram-negative bacteria. LPS is responsible for initiating a series of highly complex cascading events leading to multiple organ damage. Reactive oxygen species are also thought to play an important role as an end-effector molecule. We examined the role of HO-1 induction in the intestinal tissue injury in a rat model of septic MODS produced by intraperitoneal injection of LPS. We found that HO-1 was markedly induced following LPS treatment in the mucosal epithelial cells in the Upper intestine such as the duodenum and the jejunum, whereas HO-1 was hardly expressed and not induced by the same treatment in the lower intestine such as the ileum and the colon. In contrast, the intestinal tissue injury acid inflammation was more pronounced in the lower intestine than in the upper intestine. Pretreatment of animals with HO-1 inhibitor augmented mucosal epithelial cell injuries and inflammation in the upper intestine, but not in the lower intestine, suggesting that HO-1 induction and the maintenance of its appropriate activity appear to be critical in the protection of the intestinal epithelial cells from an oxidative injury induced by LPS, or sepsis.