Interleukin-1 regulates myeloid cell trafficking and cerebral blood flow following intracerebral haemorrhage.

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Disease Models & Mechanisms Pub Date : 2025-10-01 Epub Date: 2025-09-30 DOI:10.1242/dmm.052306
Jack Barrington, Jack Rivers-Auty, Patrick Strangward, Sabrina Tamburrano, Nikolett Lénárt, Tessa Swanton, Eloise Lemarchand, Adrian R Parry-Jones, Ádám Dénes, David Brough, Stuart M Allan
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引用次数: 0

Abstract

Intracerebral haemorrhage (ICH) is a devastating stroke subtype lacking effective therapies. Understanding key pathological processes related to acute brain damage will help deliver better outcomes for ICH. Herein, we provide evidence that myeloid cell trafficking to the parenchyma is a conserved feature of ICH in clinical and experimental settings. Consistent with others, we show that monocytes contribute to acute brain damage following collagenase-induced murine ICH. Using RNA sequencing, we identified the pro-inflammatory cytokine interleukin-1 (IL-1) as a potential upstream regulator of the acute inflammatory response, with histological data pinpointing mononuclear phagocytes as the principal cellular source of IL-1 in patient and animal tissue. In agreement, inhibition of IL-1 receptor 1 (IL-1R1) with IL-1 receptor antagonist reduced recruitment of myeloid cells. However, IL-1R1 inhibition also worsened neuromotor outcomes and reduced cerebral blood flow to the affected hemisphere. Thus, we reveal dichotomous actions of IL-1-dependent inflammation following brain haemorrhage. Although IL-1 regulates myeloid cell trafficking, it also appears to regulate cerebral blood flow. Therefore, further investigation into the consequences of IL-1 signalling following brain haemorrhage is required to clarify future therapeutic options.

白细胞介素-1调节脑出血后髓细胞运输和脑血流。
脑出血是一种破坏性的脑卒中亚型,缺乏有效的治疗方法。了解与急性脑损伤相关的关键病理过程将有助于为脑出血提供更好的结果。在此,我们提供的证据表明,髓细胞运输到实质是脑出血的一个保守特征,在临床和实验设置。与其他人一致,我们显示单核细胞有助于急性脑损伤后胶原酶诱导的小鼠脑出血。利用RNA-seq,我们发现促炎细胞因子白细胞介素-1 (IL-1)是急性炎症反应的潜在上游调节剂,组织学数据明确指出单个核吞噬细胞是患者和动物组织中IL-1的主要细胞来源。与此一致的是,用IL-1受体拮抗剂(IL-1Ra)抑制IL-1受体1 (IL-1R1)可减少髓细胞的募集。然而,IL-1R1抑制也会使神经运动结果恶化,并减少影响半球的脑血流量(CBF)。因此,我们揭示了脑出血后il -1依赖性炎症的双重作用。尽管IL-1调节髓细胞运输,它似乎也调节CBF。因此,需要进一步研究IL-1信号在脑出血后的影响,以明确未来的治疗选择。
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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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