Neuroinflammatory Mechanisms of Adult Sepsis-Associated Encephalopathy: Implications for Blood–Brain Barrier Disruption and Oxidative Stress

Abstract

Sepsis is a syndrome of life-threatening acute organ dysfunction caused by a dysregulated host response to infection. Sepsis-associated encephalopathy (SAE) refers to the diffuse brain dysfunction observed in sepsis cases, clinically characterized by a spectrum of neuropsychiatric manifestations ranging from delirium to coma. SAE is independently associated with increased short-term mortality and long-term neurological abnormalities, with currently no effective preventive or treatment strategies. The pathogenesis is intricate, involving disruptions in neurotransmitters, blood–brain barrier (BBB) breakdown, abnormal brain signal transmission, and oxidative stress, among others. These mechanisms interact or act in conjunction, contributing to the complexity of SAE. Scholars worldwide have made significant strides in understanding the pathogenesis of SAE, offering new perspectives for diagnosis and treatment. This review synthesizes recent mechanistic breakthroughs and clinical evidence to guide future research directions, particularly in targeting BBB restoration and oxidative stress.