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Immune pathway activation in neurons triggers neural damage after stroke

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机构： [1]Clinical Medicine Center, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangdong 528000, China [2]Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China [3]Clinical Medicine Center, The First People’s Hospital of Yunnan Province, Kunming, Yunnan 650032, China [4]Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA [5]Life Science Institution, Jinzhou Medical University, Jinzhou 121000, China [6]Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA [7]Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [8]Research Institute of Fudan University in Ningbo, Zhejiang 315336, China

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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.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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大类 | 1 区

生物学

小类 | 2 区细胞生物学

最新[2023]版：

大类 | 1 区

生物学

小类 | 2 区细胞生物学

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出版当年[2022]版：

Q1 CELL BIOLOGY

最新[2023]版：

Q1 CELL BIOLOGY

影响因子： 7.5 最新[2023版] 8.5 最新五年平均 8.8 出版当年[2022版] 9.9 出版当年五年平均 9.995 出版前一年[2021版] 7.5 出版后一年[2023版]

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第一作者机构： [1]Clinical Medicine Center, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangdong 528000, China

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通讯机构： [2]Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China [4]Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA [7]Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [8]Research Institute of Fudan University in Ningbo, Zhejiang 315336, China

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