Central role of microglia in sepsis-associated encephalopathy: From mechanism to therapy

Abstract

Sepsis-associated encephalopathy (SAE) is a cognitive impairment associated with sepsis that occurs in the absence of direct infection in the central nervous system or structural brain damage. Microglia are thought to be macrophages of the central nervous system, devouring bits of neuronal cells and dead cells in the brain. They are activated in various ways, and microglia-mediated neuroinflammation is characteristic of central nervous system diseases, including SAE. Here, we systematically described the pathogenesis of SAE and demonstrated that microglia are closely related to the occurrence and development of SAE. Furthermore, we comprehensively discussed the function and phenotype of microglia and summarized their activation mechanism and role in SAE pathogenesis. Finally, this review summarizes recent studies on treating cognitive impairment in SAE by blocking microglial activation and toxic factors produced after activation. We suggest that targeting microglial activation may be a putative treatment for SAE.

β-patchoulene alleviates cognitive dysfunction in a mouse model of sepsis associated encephalopathy by inhibition of microglia activation through Sirt1/Nrf2 signaling pathway

“…The restoration of phenotypic equilibrium at inflammatory site was likely to facilitate the inhibition of neuroinflammation cascade, which in turn preserved the blood-brain barrier integrity and neuronal cell function. This was inconsistent with the previous studies demonstrating that modulation of microglia activation and polarization seemed to be a feasible approach for SAE treatment [8].…”

“…Microglia plays a crucial role in orchestrating the immune response in the central nervous system(CNS) during sepsis. Upon stimulation by bacterial products or cytokines, microglial cells activate and present morphological, immunological and metabolic alterations [7,8]. Activated microglial cells are very plastic and may exist in multiple phenotypes, ranging from pro-inflammatory(M1) cell population releasing nitric oxide, TNF-α and IL-1β to antiinflammatory subtype releasing IL-10 or IL-4.…”

Clinical Phenotypes of Sepsis-Associated Encephalopathy: A Retrospective Cohort Study

“…Of the 2,780 patients with SAE, 57% were male and had median age of 67 years (56-76.8) (Table 1). The median GCS score was 12 (8)(9)(10)(11)(12)(13)(14) and the median SOFA score was 6 (4-9). The overall in-hospital mortality was 23% (95% CI, 0.21-0.25).…”

“…In general, patients in the ischemic-hypoxic and metabolic phenotypes were more critically ill than those in unclassified phenotype. The mixed phenotype was associated with a worse GCS score (median 10 [6-13] vs. 13 [9][10][11][12][13][14]), higher SOFA score (median 9 [6][7][8][9][10][11][12] vs. 5 [3][4][5][6][7]) and more severe biological parameters than the unclassified phenotype (Table 2). Among all infection sources, pulmonary infections occurred in 1272 of SAE patients (46%).…”

“…According to broad diagnostic criteria, the incidence of SAE reporting varies fairly from 9% to 76% (2)(3)(4). Its pathophysiology comprises neuroinflammation (5,6), cerebral ischemia (7), and metabolic disturbances (8,9). Given the heterogeneity of conditions involved, specific therapeutic targets for brain dysfunction in sepsis remain limited.…”