Microglia and neuroinflammation: the key drivers of sepsis-associated encephalopathy

Abstract

Sepsis is a serious global health issue, and sepsis-associated encephalopathy (SAE) is one of the early complications of sepsis, with symptoms including neuronal and synaptic dysfunction, cognitive dysfunction and brain damage. Neuroinflammation has been identified as a significant pathogenic mechanism in the context of SAE, and microglia, as resident immune cells in the brain, playing a pivotal role in the development and progression of SAE by regulating unbalanced neuroinflammation. It is evident that microglia manifest heterogeneous characteristics at all stages of SAE. The basis for this heterogeneity is the alteration in gene expression profiles with the progression of the disease. This article reviews the recent progress of research on neuroinflammation in SAE and elucidate the specific changes in the function, phenotype, and gene expression profiles of microglia in SAE, revealing how microglia are involved in the onset and progression of SAE through regulating neuroinflammation. Finally, this review provides a comprehensive overview of the current therapeutic options for SAE, with a particular focus on the targeting of microglia and the neuroinflammation mediated by them, and puts forward the shortcomings and perspectives of the current research related to microglia and the neuroinflammation mediated by them in SAE, thus offering valuable insights for the development of relevant drugs and the subsequent advancement of basic research in this field.