1. Immune pathway activation in neurons triggers neural damage after stroke
- Author
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Dong-mei Wu, Ji-ping Liu, Jie Liu, Wei-hong Ge, Su-zhen Wu, Chi-jia Zeng, Jia Liang, KeJian Liu, Quan Lin, Xiao-wu Hong, Yi Eve Sun, and Jun Lu
- Subjects
CP: Neuroscience ,CP: Immunology ,Biology (General) ,QH301-705.5 - Abstract
Summary: Ischemic brain injury is a severe medical condition with high incidences in elderly people without effective treatment for the resulting neural damages. Using a unilateral mouse stroke model, we analyze single-cell transcriptomes of ipsilateral and contralateral cortical penumbra regions to objectively reveal molecular events with single-cell resolution at 4 h and 1, 3, and 7 days post-injury. Here, we report that neurons are among the first cells that sense the lack of blood supplies by elevated expression of CCAAT/enhancer-binding protein β (C/EBPβ). To our surprise, the canonical inflammatory cytokine gene targets for C/EBPβ, including interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), are subsequently induced also in neuronal cells. Neuronal-specific silencing of C/EBPβ or IL-1β and TNF-α substantially alleviates downstream inflammatory injury responses and is profoundly neural protective. Taken together, our findings reveal a neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury.
- Published
- 2023
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