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Journal of Neuroinflammation

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01-12-2020 | Hypoxic-Ischemic Brain Injury | Research

Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury

Authors: Mengya Jiao, Xiangyong Li, Liying Chen, Xiaodi Wang, Baohong Yuan, Tao Liu, Qun Dong, Hanfang Mei, Hui Yin

Published in: Journal of Neuroinflammation | Issue 1/2020

Abstract

Background

Interleukin-33 (IL-33) is a well-recognized pleiotropic cytokine which plays crucial roles in immune regulation and inflammatory responses. Recent studies suggest that IL-33 and its receptor ST2 are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IL-33/ST2 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action.

Methods

The brain HI model was established in neonatal C57BL/6 mice by left common carotid artery occlusion with 90 min hypoxia and treated with IL-33 at a dose of 0.2 μg/day i.p. for 3 days. TTC staining and neurobehavioral observation were used to evaluate the HI brain injury. Immunofluorescence and flow cytometry were applied to determine the expression of IL-33 and its receptor ST2 on brain CNS cells and cell proliferation and apoptosis. OGD experiment was used to assay the viability of astrocytes and neurons. RT-qPCR was used to measure the expression of neurotrophic factor-associated genes.

Results

The expression level of IL-33 was markedly enhanced in astrocytes 24 h after cerebral HI in neonatal mice. Exogenous delivery of IL-33 significantly alleviated brain injury 7 days after HI, whereas ST2 deficiency exacerbated brain infarction and neurological deficits post HI. Flow cytometry analyses demonstrated high levels of ST2 expression on astrocytes, and the expression of ST2 was further elevated after HI. Intriguingly, IL-33 treatment apparently improved astrocyte response and attenuated HI-induced astrocyte apoptosis through ST2 signaling pathways. Further in vitro studies revealed that IL-33-activated astrocytes released a series of neurotrophic factors, which are critical for raising neuronal survival against oxygen glucose deprivation.

Conclusions

The activation of IL-33/ST2 signaling in the ischemic brain improves astrocyte response, which in turn affords protection to ischemic neurons in a glial-derived neurotrophic factor-dependent manner.

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Title: Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury
Authors: Mengya Jiao
Xiangyong Li
Liying Chen
Xiaodi Wang
Baohong Yuan
Tao Liu
Qun Dong
Hanfang Mei
Hui Yin
Publication date: 01-12-2020
Publisher: BioMed Central
Keyword: Hypoxic-Ischemic Brain Injury
Published in: Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-020-01932-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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