Dataset Information
Netrin-1 attenuates brain injury after middle cerebral artery occlusion via downregulation of astrocyte activation in mice.
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ABSTRACT: Background
Netrin-1 functions largely via combined receptors and downstream effectors. Evidence has shown that astrocytes express netrin-1 receptors, including DCC and UNC5H2. However, whether netrin-1 influences the function of astrocytes was previously unknown.Methods
Lipopolysaccharide was used to stimulate the primary cultured astrocytes; interleukin release was used to track astrocyte activation. In vivo, shRNA and netrin-1 protein were injected in the mouse brain. Infarct volume, astrocyte activation, and interleukin release were used to observe the function of netrin-1 in neuroinflammation and brain injury after middle cerebral artery occlusion.Results
Our results demonstrated that netrin-1 reduced lipopolysaccharide-induced interleukin-1? and interleukin-12? release in cultured astrocytes, and blockade of the UNC5H2 receptor with an antibody reversed this effect. Additionally, netrin-1 increased p-AKT and PPAR-? expression in primary cultured astrocytes. In vivo studies showed that knockdown of netrin-1 increased astrocyte activation in the mouse brain after middle cerebral artery occlusion (p?3, p?ConclusionOur results indicate that netrin-1 is an important molecule in regulating astrocyte activation and neuroinflammation in cerebral ischemia and provides a potential target for ischemic stroke therapy.
SUBMITTER: He X
PROVIDER: S-EPMC6145326 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Netrin-1 attenuates brain injury after middle cerebral artery occlusion via downregulation of astrocyte activation in mice.
Journal of neuroinflammation 20180918 1
<h4>Background</h4>Netrin-1 functions largely via combined receptors and downstream effectors. Evidence has shown that astrocytes express netrin-1 receptors, including DCC and UNC5H2. However, whether netrin-1 influences the function of astrocytes was previously unknown.<h4>Methods</h4>Lipopolysaccharide was used to stimulate the primary cultured astrocytes; interleukin release was used to track astrocyte activation. In vivo, shRNA and netrin-1 protein were injected in the mouse brain. Infarct v ...[more]
