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Dexamethasone downregulates the expressions of MMP-9 and oxidative stress in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection

Published online by Cambridge University Press:  02 October 2020

Hung-Chin Tsai Open the ORCID record for Hung-Chin Tsai [Opens in a new window]  and
Yu-Hsin Chen
Hung-Chin Tsai*
Affiliation:
Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan National Yang-Ming University, Taipei, Taiwan Department of Parasitology and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
Yu-Hsin Chen
Affiliation:
Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan National Yang-Ming University, Taipei, Taiwan
*
Author for correspondence: Hung-Chin Tsai, E-mail: hctsai1011@yahoo.com.tw
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Abstract

Steroids have been shown to be beneficial in patients and mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection; however, the mechanism for this beneficial effect is unknown. We speculated that the effect of steroids in eosinophilic meningitis caused by A. cantonensis infection may be mediated by the downregulation of matrix metallopeptidase-9 (MMP-9) and oxidative stress pathways via glucocorticoid receptors (GRs). We found blood–brain barrier (BBB) dysfunction in mice with eosinophilic meningitis 2–3 weeks after infection as evidenced by increased extravasation of Evans blue and cerebrospinal fluid (CSF) albumin levels. The administration of dexamethasone significantly decreased the amount of Evans blue and CSF albumin. The effect of dexamethasone was mediated by GRs and heat shock protein 70, resulting in subsequent decreases in the expressions of nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in the CSF and brain parenchymal after 2 weeks of steroid administration. Steroid treatment also decreased CSF/brain homogenate MMP-9 concentrations, but had no effect on CSF MMP-2 levels, indicating that MMP-9 rather than MMP-2 played a major role in BBB dysfunction in mice with eosinophilic meningitis. The concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) gradually increased after 1–3 weeks of infection, and the administration of dexamethasone significantly downregulated the concentration of oxidized derivative 8-OHdG in CSF. In conclusion, increased 8-OHdG and MMP-9 concentrations were found in mice with eosinophilic meningitis caused by A. cantonensis infection. The effect of dexamethasone was mediated by GRs and significantly decreased not only the levels of 8-OHdG and MMP-9 but also NF-κB, JNK and ERK.

Keywords

Angiostrongylus cantonensiscorticosteroideosinophilic meningitisoxidative stress
Type
Research Article
Information
Parasitology , Volume 148 , Special Issue 2: 6th International Workshop on Angiostrongylus and Angiostrongyliasis, Hilo, Hawai'i, USA, January, 2020 , February 2021 , pp. 187 - 197
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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