Mechanisms of Blood-Brain Barrier Disruption in Herpes Simplex Encephalitis

Abstract

Herpes simplex encephalitis (HSE) is often caused by infection with herpes simplex virus 1 (HSV-1), a neurotropic double-stranded DNA virus. HSE infection always impacts the temporal and frontal lobes or limbic system, leading to edema, hemorrhage, and necrotic changes in the brain parenchyma. Additionally, patients often exhibit severe complications following antiviral treatment, including dementia and epilepsy. HSE is further associated with disruptions to the blood-brain barrier (BBB), which consists of microvascular endothelial cells, tight junctions, astrocytes, pericytes, and basement membranes. Following an HSV-1 infection, changes in BBB integrity and permeability can result in increased movement of viruses, immune cells, and/or cytokines into the brain parenchyma. This leads to an enhanced inflammatory response in the central nervous system and further damage to the brain. Thus, it is important to protect the BBB from pathogens to reduce brain damage from HSE. Here, we discuss HSE and the normal structure and function of the BBB. We also discuss growing evidence indicating an association between BBB breakdown and the pathogenesis of HSE, as well as future research directions and potential new therapeutic targets. Graphical Abstract During herpes simplex encephalitis, the functions and structures of each composition of BBB have been altered by different factors, thus the permeability and integrity of BBB have been broken. The review aim to explore the potential mechanisms and factors in the process, probe the next research targets and new therapeutic targets.

Keywords: Blood-brain barrier; Herpes simplex encephalitis; Immune response; Microglia; Tight junctions.