Immune pathway activation in neurons triggers neural damage after stroke
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,
Jun Lu
Affiliations
Dong-mei Wu
Clinical Medicine Center, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangdong 528000, China
Ji-ping Liu
Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
Jie Liu
Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China; Clinical Medicine Center, The First People’s Hospital of Yunnan Province, Kunming, Yunnan 650032, China
Wei-hong Ge
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Su-zhen Wu
Clinical Medicine Center, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangdong 528000, China
Chi-jia Zeng
Clinical Medicine Center, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangdong 528000, China
Jia Liang
Life Science Institution, Jinzhou Medical University, Jinzhou 121000, China
KeJian Liu
Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
Quan Lin
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Xiao-wu Hong
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Research Institute of Fudan University in Ningbo, Zhejiang 315336, China; Corresponding author
Yi Eve Sun
Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Corresponding author
Jun Lu
Clinical Medicine Center, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangdong 528000, China; Corresponding author
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.
