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Mechanisms of Blood-Brain Barrier Disruption in Herpes Simplex Encephalitis

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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.

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.

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Abbreviations

TJs:

tight junctions

AJ:

adhesion junction

BM:

basal membrane

BBB:

blood-brain barrier

CNS:

central nervous system

EAE:

experimental autoimmune encephalomyelitis

EC:

endothelial cells

ECM:

extracellular molecules

GA:

Golgi apparatus

HSE:

Herpes simplex encephalitis

HSV-1:

herpes simplex virus 1

ICAM:

intracellular adhesion molecule

IFN:

interferon

IL-1β:

interleukin 1-beta

iNOS:

inducible nitric oxide synthase

MMP:

Membrane metalloprotease

NF-κB:

nuclear factor kappa B

PKC:

protein kinase C

TEER:

transendothelial electric resistance

TNF-α:

tumor necrosis factor alpha

TGF-β:

transforming growth factor-beta

VEGF:

vascular endothelial growth factor

ZO:

zonula occluden.

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Acknowledgements

This study was supported by the National Natural Science Foundation (Grant 81571181) of China P.R. HL carried out the literature review and drafted the manuscript. KQ and QH helped to draft the manuscript. QL conceived of, designed, and coordinated the study. WL contributed to and finalized the draft. All authors read and approved the final manuscript.

Funding

This study was supported by the National Natural Science Foundation (Grant 81571181) of China P.R.

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  1. Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China

    Hui Liu, Ke Qiu, Qiang He, Qiang Lei & Wei Lu

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  1. Hui Liu
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Liu, H., Qiu, K., He, Q. et al. Mechanisms of Blood-Brain Barrier Disruption in Herpes Simplex Encephalitis. J Neuroimmune Pharmacol 14, 157–172 (2019). https://doi.org/10.1007/s11481-018-9821-6

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