Research progress on sepsis-associated encephalopathy by inhibiting pyroptosis

Sepsis is a life-threatening condition characterized by multiple organ dysfunction syndrome resulted from dysregulated host responses to infection. Sepsis-associated encephalopathy (SAE) is one of the most common symptoms of acute-phase sepsis, with nearly 70 % of patients with sepsis ultimately developing SAE. Pyroptosis represents a type of cell death that is initiated by inflammation. This cell death type is associated with various infectious and noninfectious diseases. The gasdermin family proteins are crucial cell death executors and critical components in regulating the canonical pyroptosis pathway in microglia. In this review, we summarize the inhibitory effects of several drugs and genes on the pyroptosis pathway. Our findings suggest that several drugs (puerarin, VX765, HC067047, dexpramipexole, and Danhong injection), erbin gene, and TRIM45 knockdown improve SAE by suppressing the canonical pathway of NLRP3/caspase-1/gasdermin D-mediated pyroptosis. Therefore, they have significant importance in terms of brain protection. Moreover, we review the relevant literature published in recent years and summarize the research status and development prospects in this field to provide a basis for subsequent related research.