Ex vivo imaging and analysis of ROS generation correlated with microglial activation in rat model with acute neuroinflammation induced by intrastriatal injection of LPS.
Acute Disease
Animals
Brain
/ drug effects
Disease Models, Animal
Ethidium
/ analogs & derivatives
Fluorescent Dyes
/ chemistry
Free Radical Scavengers
/ pharmacology
Lipopolysaccharides
Male
Microglia
/ cytology
Minocycline
/ pharmacology
Neuroinflammatory Diseases
/ chemically induced
Optical Imaging
/ methods
Rats, Wistar
Reactive Oxygen Species
/ metabolism
Thiourea
/ analogs & derivatives
Brain
Fluorescence imaging
Lipopolysaccharide
Microglia
Reactive oxygen species
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
20 12 2021
20 12 2021
Historique:
received:
01
09
2021
accepted:
02
11
2021
pubmed:
16
11
2021
medline:
4
1
2022
entrez:
15
11
2021
Statut:
ppublish
Résumé
Neuroinflammation and oxidative stress are hallmarks of neurodegenerative diseases. Microglia, the major important regulators of neuroinflammation, are activated in response to excessive generation of reactive oxygen species (ROS) from damaged cells and resulting in elevated and sustained damages. However, the relationship between microglia and ROS-regulatory system in the early stages of neuroinflammation prior to the appearance of neuronal damages have not been elucidated in detail. In this study, we analyzed the time-dependent changes in ROS generation during acute neuroinflammation in rats that were given an intrastriatal injection of lipopolysaccharide (LPS). We evaluated the effects of minocycline, an anti-inflammatory antibiotic, and N,N'-dimethylthiourea (DMTU), a radical scavenger, to understand the correlation between activated microglia and ROS generation. Ex vivo fluorescence imaging using dihydroethidium (DHE) clearly demonstrated an increased ROS level in the infused side of striatum in the rats treated with LPS. The level of ROS was changed in time-dependent manner, and the highest level of ROS was observed on day 3 after the infusion of LPS. Immunohistochemical studies revealed that time-dependent changes in ROS generation were well correlated to the presence of activated microglia. The inhibition of microglial activation by minocycline remarkably reduced ROS levels in the LPS-injected striatum, which indicated that the increased ROS generation caused by LPS was induced by activated microglia. DMTU decreased ROS generation and resulted in remarkable inhibitory effect on microglial activation. This study demonstrated that ROS generation during acute neuroinflammation induced by LPS was considerably associated with microglial activation, in an intact rat brain. The results provides a basis for understanding the interaction of ROS-regulatory system and activated microglia during neuroinflammation underlying neurodegenerative diseases.
Identifiants
pubmed: 34781201
pii: S0006-291X(21)01511-4
doi: 10.1016/j.bbrc.2021.11.008
pii:
doi:
Substances chimiques
Fluorescent Dyes
0
Free Radical Scavengers
0
Lipopolysaccharides
0
Reactive Oxygen Species
0
dihydroethidium
104821-25-2
1,3-dimethylthiourea
8P30PMD17W
Ethidium
EN464416SI
Minocycline
FYY3R43WGO
Thiourea
GYV9AM2QAG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101-106Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no competing of interest.