A review on pathological implications and therapeutic interventions of sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) is a serious form of acute cerebral dysfunction that is seen in the ICU and is characterised by high mortality and long-term neuropsychiatric disabilities. This condition is not caused by a direct central nervous system infection; instead, it develops through a complex cascade of the systemic inflammatory response involving cytokine release, mitochondrial dysfunction, oxidative damage, and disruption of the blood-brain barrier. Since there are no approved drugs that specifically protect the brain during the development of SAE, natural and synthetic compounds that modulate a variety of target sites offer a highly attractive therapeutic option. This review integrates preclinical findings from rodent models of SAE induced by lipopolysaccharide (LPS) and cecal-ligation-and-puncture (CLP) models. The findings suggest that certain plant-derived phytochemicals, along with various investigational agents, have effective neuroprotective activity and target the complex pathophysiology of SAE in a multi-faceted manner. These bioactive compounds efficiently suppress neuroinflammatory responses, the production of reactive species, disruption of the blood-brain barrier, and apoptosis of neuronal cells in these experimental models. These data firmly suggest that the multi-target nature of these molecules makes them highly appropriate for the treatment of SAE. Extensive translational research is now required to confirm these promising findings in human septic patient populations.