Reactive Microgliosis in Sepsis-Associated and Acute Hepatic Encephalopathies: An Ultrastructural Study

Abstract

Sepsis and acute liver failure are associated with severe endogenous intoxication. Microglia, which are the resident immune brain cells, play diverse roles in central nervous system development, surveillance, and defense, as well as contributing to neuroinflammatory reactions. In particular, microglia are fundamental to the pathophysiology of reactive toxic encephalopathies. We analyzed microglial ultrastructure, morphotypes, and phagocytosis in the sensorimotor cortex of cecal ligation and puncture (CLP) and acetaminophen-induced liver failure (AILF) Wistar rats. A CLP model induced a gradual shift of ~50% of surveillant microglia to amoeboid hypertrophic-like and gitter cell-like reactive phenotypes with active phagocytosis and frequent contacts with damaged neurons. In contrast, AILF microglia exhibited amoeboid, rod-like, and hypertrophic-like reactive morphotypes with minimal indications for efficient phagocytosis, and were mostly in contact with edematous astrocytes. Close interactions of reactive microglia with neurons, astrocytes, and blood–brain barrier components reflect an active contribution of these cells to the tissue adaptation and cellular remodeling to toxic brain damage. Partial disability of reactive microglia may affect the integrity and metabolism in all tissue compartments, leading to failure of the compensatory mechanisms in acute endogenous toxic encephalopathies.