ID 6572
File
Authors
Kurata, Hirofumi Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University / Division of Child Neurology, Department of Brain and Neurosciences, Tottori University / Department of Pediatrics, National Hospital Organization, Kumamoto Saishunso National Hospital Researchers DB KAKEN
Saito, Kengo Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University
Kawashima, Fumiaki Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University
Ikenari, Takuya Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University
Oguri, Masayoshi Department of Pathobiological Science and Technology, School of Health Science, Faculty of Medicine, Tottori University Researchers DB
Saito, Yoshiaki Division of Child Neurology, Department of Brain and Neurosciences, Tottori University Researchers DB KAKEN
Maegaki, Yoshihiro Division of Child Neurology, Department of Brain and Neurosciences, Tottori University Researchers DB KAKEN
Mori, Tetsuji Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University Researchers DB KAKEN
Keywords
Hyperthermia
lipopolysaccharide
seizure
blood–brain barrier
vasogenic edema
acute encephalopathy
Abstract
Acute encephalopathy (AE) is mainly reported in East Asia and, in most cases, results from pediatric viral infections, leading to fever, seizure, and loss of consciousness. Cerebral edema is the most important pathological symptom of AE. At present, AE is classified into four categories based on clinical and pathophysiological features, and cytokine storm-induced AE is the severest among them. The pathogenesis of AE is currently unclear; this can be attributed to the lack of a simple and convenient animal model for research. Here, we hypothesized that the induction of systemic inflammation using lipopolysaccharide (LPS) injection followed by hyperthermia (HT) treatment can be used to develop an animal model of cytokine storm-induced AE. Postnatal eight-day-old mouse pups were intraperitoneally injected with low-dose LPS (50 or 100 µg/kg) followed by HT treatment (41.5°C, 30 min). Histological analysis of their brains was subsequently performed. Fluorescein isothiocyanate assay combined with immunohistochemistry was used to elucidate blood–brain barrier (BBB) disruption. LPS (100 µg/kg) injection followed by HT treatment increased BBB permeability in the cerebral cortex and induced microglial activation. Astrocytic clasmatodendrosis was also evident. The brains of some pups exhibited small ischemic lesions, particularly in the cerebral cortex. Our results indicate that a low-dose LPS injection followed by HT treatment can produce symptoms of cytokine storm-induced AE, which is observed in diseases, such as acute necrotizing encephalopathy and hemorrhagic shock and encephalopathy syndrome. Thus, this mouse model can help to elucidate the pathogenetic mechanisms underlying AE.
Publisher
Society for Experimental Biology and Medicine
Content Type
Journal Article
Link
ISSN
15353702
NCID
AA11503891
Journal Title
Experimental biology and medicine
Volume
244
Issue
9
Start Page
743
End Page
751
Journal Section
Research Article
Published Date
2019-05-02
Publisher-DOI
Text Version
Author
Rights
Copyright © 2019 by the Society for Experimental Biology and Medicine.
Citation
This research was published by the Society for Experimental Biology and Medicine: Kurata, H., Saito, K., Kawashima, F., Ikenari, T., Oguri, M., Saito, Y., … Mori, T. (2019). Developing a mouse model of acute encephalopathy using low-dose lipopolysaccharide injection and hyperthermia treatment. Experimental Biology and Medicine, 244(9), pp.743–751. Copyright © 2019 by the Society for Experimental Biology and Medicine. DOI: 10.1177/1535370219846497.
Department
Faculty of Medicine/Graduate School of Medical Sciences/University Hospital
Language
English