缺血性脑损伤是一种严重的疾病，在老年人中发病率很高，而无法有效治疗由此造成的神经损伤。使用单侧小鼠中风模型，我们分析同侧和对侧皮质半影区域的单细胞转录组，以客观地揭示损伤后 4 小时以及 1、3 和 7 天的单细胞分辨率分子事件。在此，我们报告神经元是最早通过 CCAAT/增强子结合蛋白 β (C/EBPβ) 表达升高来感知血液供应缺乏的细胞之一。令我们惊讶的是，C/EBPβ 的典型炎症细胞因子基因靶标，包括白介素-1β (IL-1β) 和肿瘤坏死因子 α (TNF-α)，随后也在神经元细胞中被诱导。 C/EBPβ 或 IL-1β 和 TNF-α 的神经元特异性沉默可显着减轻下游炎症损伤反应，并具有深刻的神经保护作用。总而言之，我们的研究结果揭示了缺血性脑损伤早期病理触发的神经元炎症机制。版权所有 © 2023 作者。由爱思唯尔公司出版。保留所有权利。

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.