Our fucking failures of stroke associations will DO NOTHING. Your doctor will DO NOTHING. Your stroke hospital will DO NOTHING. You're screwed.
https://www.sciencedirect.com/science/article/pii/S2211124718303401
Highlights
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- Microglial ZEB1 is upregulated after acute brain ischemia induced by tMCAO
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- Targeted overexpression of microglial ZEB1 reduces acute ischemic brain injury
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- Microglial ZEB1 regulates the immune response in the CNS after ischemic stroke
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- Microglia ZEB1 inhibits the CXCL1 secretion from astrocytes through TGF-β1 pathway
Summary
Microglia are a key immune-competent cell type that respond to environmental and physiological changes during ischemic stroke. However, the molecular mechanisms controlling post-ischemic microglia activity are unclear. Understanding these mechanisms may ultimately reduce disease burden and allow the manipulation of microglia responses to shape the outcomes of stroke. Here, we report that, after experimentally induced stroke, ZEB1 is highly expressed in ipsilateral cerebral hemisphere, where it is upregulated mainly in microglia. Using a conditional transgenic mouse, we found that ZEB1 upregulation in microglia regulates immune responses in the CNS and alleviates brain injury after ischemic stroke. Our data indicate that ZEB1 overexpression mediates microglia responses and, in turn, inhibits the production of astrocytic CXCL1 through the TGF-β1-dependent pathway. Reduced CXCL1 leads to a decline in neutrophil infiltration into the brain, thereby reducing CNS inflammation. Our results demonstrate the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggest a potential means for reducing stroke-induced neurological injury.
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