Sepsis and its complications are the leading causes of mortality in intensive care units accounting for 10–50% of deaths. Up to 71% of septic patients develop potentially irreversible acute cerebral dysfunction. This sepsis-induced encephalopathy is caused by systemic inflammation in the absence of direct brain infection and clinically characterized by slowing of mental processes, impaired attention, disorientation, delirium or coma. Importantly, septic encephalopathy is an early sign of sepsis and associated with an increased rate of morbidity and mortality.

The pathogenesis of septic encephalopathy is unlikely to be directly induced by a pathogenic toxin, as similar encephalopathy can develop as a result of a number of systemic inflammatory response syndromes that lack an infectious etiology (e.g. acute pancreatitis, burns etc.).

Clinical and experimental data suggest that a number of factors including the local generation of pro-inflammatory cytokines, impaired cerebral microcirculation, an imbalance of neurotransmitters and a negative impact of peripheral organ failure contribute to the development of SE.

Selected Publications:

Schlachetzki JC, Fiebich BL, Haake E, de Oliveira AC, Candelario-Jalil E, Heneka MT, Hüll M. Norepinephrine enhances the LPS-induced expression of COX-2 and secretion of PGE2 in primary rat microglia. J Neuroinflammation. 2010 Jan 11;7:2. PMID: 20064241

Weberpals M, Hermes M, Hermann S, Kummer MP, Terwel D, Semmler A, Berger M, Schäfers M, Heneka MT. NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J Neurosci. 2009 Nov 11;29(45):14177-84. PMID:19906966

Semmler A, Hermann S, Mormann F, Weberpals M, Paxian SA, Okulla T, Schäfers M, Kummer MP, Klockgether T, Heneka MT. Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism. J Neuroinflammation. 2008 Sep 15;5:38.PMID:18793399

Funding