Sepsis-associated encephalopathy: Autophagy and miRNAs regulate microglial activation

Abstract

Sepsis-associated encephalopathy (SAE) describes diffuse or multifocal cerebral dysfunction caused by the systemic inflammatory response to sepsis. SAE is a common neurological complication in patients in the middle and late stages of sepsis in the intensive care unit. Microglia, resident macrophages of the central nervous system, phagocytose small numbers of neuronal cells and apoptotic cells, among other cells, to maintain the dynamic balance of the brain's internal environment. The neuroinflammatory response induced by activated microglia plays a central role in the pathogenesis of various central nervous system diseases. In this paper, we systematically describe the functions and phenotypes of microglia, summarize how microglia mediate neuroinflammation and contribute to the occurrence and development of SAE, and discuss recent progress in autophagy- and microRNA-mediated regulation of microglial activation to provide a theoretical basis for the prevention and treatment of SAE and identify related therapeutic targets.

Keywords: autophagy; microRNA; microglia; neuroinflammation; sepsis-associated encephalopathy.

FIGURE 1

Microglia are polarized toward the M1 and M2 phenotypes by endogenous or exogenous stimuli. M1 microglia releases proinflammatory factors, proinflammatory chemokines, oxidative products, etc., to exacerbate neuroinflammation; inflammatory cytokines and oxidative products in turn further activate microglia and promote blood–brain barrier disruption. M2 microglia exert neuroprotective effects and phagocytose cell debris and misfolded proteins while releasing anti‐inflammatory factors and neurotrophic factors to promote neuronal healing and neurological function recovery.

FIGURE 2

MicroRNA‐mediated regulation of autophagy affects microglial activation, (1) microRNAs promote autophagy, thereby inhibiting microglial activation, and (2) microRNAs inhibit autophagy, thereby promoting microglial activation. Exacerbation of neuroinflammatory responses contributes to the development of SAE. SAE, sepsis‐associated encephalopathy.