1. Immune pathway activation in neurons triggers neural damage after stroke.
- Author
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Wu DM, Liu JP, Liu J, Ge WH, Wu SZ, Zeng CJ, Liang J, Liu K, Lin Q, Hong XW, Sun YE, and Lu J
- Subjects
- Humans, Mice, Animals, Aged, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Gene Expression Regulation, Neurons metabolism, Disease Models, Animal, CCAAT-Enhancer-Binding Protein-beta metabolism, Stroke genetics, Stroke metabolism, Brain Injuries metabolism
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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