Dexamethasone inhibits brain apoptosis in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection

Abstract

Background: Angiostrongylus cantonensis, the rat lungworm, is the major cause of eosinophilic meningitis worldwide. Rats serve as the definitive host of the nematode, but humans can be infected incidentally, leading to eosinophilic meningitis. A previous BALB/c animal study has demonstrated increased apoptotic proteins and decreased anti-apoptotic proteins in mice infected with A. cantonensis. Steroids may be an effective treatment option for eosinophilic meningitis caused by A. cantonensis, but the involved mechanism is unclear. This study hypothesized that the beneficial effects of steroids on eosinophilic meningitis are mediated by decreased apoptosis. Methods: In a BALB/c animal model, mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and were sacrificed every week for 3 consecutive weeks after infection or until the end of the study. Dexamethasone was injected intra-peritoneally from the 7 th day post-infection until the end of the 21-day study. Evans blue method was used to measure changes in the blood brain barrier, while western blotting, immuno-histochemistry, and TUNEL assay were used to analyze brain homogenates expression of apoptotic and anti-apoptotic proteins. Results: There were increased amounts of Evans blue, apoptotic proteins (caspase-3, -8, and -9 and cytochrome C), and decreased anti-apoptotic proteins (bcl-2) after 2-3 weeks of infection. Dexamethasone administration significantly decreased Evans blue extravasations and apoptotic protein expressions. Conclusions: Apoptosis of mice brain homogenates can be repressed by dexamethasone treatment.

Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen

“…In support of this, Morassutti et al (2013b) and Yong et al (2015a) report no evidence of Wolbachia in their genome sequences. While Foster et al (2008) suggest that the findings of Tsai et al (2007b) may be the result of contamination, it should be noted that not all specimens within a filarial nematode species harbour Wolbachia even if that species is known to possess a Wolbachia endosymbiont (Ferri et al 2011).…”

Preliminary expression profile of cytokines in brain tissue of BALB/c mice with Angiostrongylus cantonensis infection

“…In this current study, IL-4, IL-13, IL-19, IL-10, IL-6, IL-27 and IL-5 showed almost no expression in the normal control group, whilst at 14 dpi and 21 dpi, IL-4 and IL-13 significantly increased, followed by IL-19, IL-10, IL-6, IL-27 and IL-5, which were highly expressed. The migration of the worm in the brain of host induced injury and inflammation of CNS [ 42 , 43 ]. Macrophages, eosinophils and lymphocytes gathered at the site of inflammation and Th2-type cytokine secretion such as IL-4, IL-5, IL-10, and IL-13 were increased under the stimulation of worm antigen in the late infection phase.…”

Dexamethasone Downregulates Expressions of 14-3-3β and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection

“…IL-5, a hemopoietic factor, has been shown to stimulate the proliferation, differentiation, and maturation of eosinophils [29], and an increased CSF IL-5 level and eosinophilia have been reported in eosinophilic meningitis caused by A. cantonensis infection [13,30]. Steroids have been found to induce the apoptosis of eosinophils [31] and inhibit brain apoptosis in mice with eosinophilic meningitis [11]. Taken together, the beneficial effects of steroids on eosinophilic meningitis caused by A. cantonensis infection in this study may have been mediated by improvements in BBB dysfunction, inhibition of the expressions of plasminogen activators and inflammation, down-regulation of 14-3-3 isoform proteins in the CSF, inhibition of mice brain apoptosis, and other unidentified mechanisms.…”

“…When this parasitic infection occurs in humans and mice (non-permissive hosts), the development of the larvae will stop at the young-adult worm stage in the brain and induce eosinophilia in blood and especially in cerebrospinal fluid (CSF) [8–13]. Previous studies have shown that transmigration of eosinophils to CSF [13], brain apoptosis [11] and the overexpression of CSF 14-3-3 β [12] are associated with blood brain barrier (BBB) dysfunction in mice and humans infected with A. cantonensis .…”