Modulation of experimental herpes encephalitis-associated neurotoxicity through sulforaphane treatment.

PloS One
Scott J SchachteleJames R Lokensgard

Abstract

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane...Continue Reading

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Citations

Sep 3, 2013·Antioxidants & Redox Signaling·Claudia N Paiva, Marcelo T Bozza
Aug 21, 2013·Future Virology·Chandran RamakrishnaEdouard M Cantin
Dec 3, 2015·Experimental Neurology·Kim OhlMarkus Kipp
Mar 19, 2013·Médecine et maladies infectieuses·T B DeramaudtM Bonay
Mar 24, 2016·Veterinary Research·Liqian ZhuGuoqiang Zhu
Nov 13, 2014·Journal of Neurovirology·Christina M KolliasStephen R Jennings
Dec 8, 2015·Journal of Cellular Biochemistry·Gláubia SartoriCristina W Nogueira
Oct 17, 2018·Current Medicinal Chemistry·Jacopo AgrimiVincenzo Lionetti
Aug 14, 2020·Autoimmune Diseases·Mohammad Javad TavassolifarMaryam Izad
Dec 6, 2018·Oxidative Medicine and Cellular Longevity·Choongho Lee
Feb 14, 2020·Clinical Microbiology Reviews·Jocelyne Piret, Guy Boivin
Jul 25, 2019·Brain Circulation·Eric A Klomparens, Yuchuan Ding
Apr 24, 2020·Oxidative Medicine and Cellular Longevity·Upayan PatraMamta Chawla-Sarkar
Oct 14, 2020·Biochemical and Biophysical Research Communications·Weixing XuJing Huang

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Methods Mentioned

BETA
nuclear translocation
flow cytometry
PCR
transgenic
Assay

Software Mentioned

FlowJo
StatView

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