Neuroglia in hepatic encephalopathy

Neuroglia contribute to the pathophysiology of hepatic encephalopathy (HE) either beneficially or detrimentally. Pathogenesis of HE is linked to damage triggered by blood-derived toxins, with ammonia being the main causative factor. Neuroglial cells, especially astrocytes and microglia, respond to HE-associated systemic and central signals and undergo complex and variable changes in their metabolism, morphology, and function, which include ion and water dyshomeostasis in conjunction with neurotransmission imbalance and neuroinflammation. HE-induced alterations of astrocytes are defined as astrocytopathy, with aberrant astrocytes resulting in either gain or loss of functions. In the chronic HE, the presence of Alzheimer type II cells is a histologic hallmark, with asthenic astrocytes emerging as a newcomer. In acute HE, rapid swelling of astrocytes is a primary cause of cerebral edema and mortality. This chapter reviews the dominant role of astrocytes in the pathogenesis of HE resulting from acute and chronic liver failure, mainly in experimental models. The focus is on the loss of homeostatic function bearing upon the functioning of the glymphatic system, aberrant neurotransmission as a consequence of astrocyte-neuron miscommunication, and the concordant neuroinflammatory response of astrocytes and microglia. The chapter concludes with a delineation of concepts for future research.