REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1643524
This article is part of the Research TopicNeuroinflammation: Mechanisms and Therapeutic InterventionsView all 18 articles
Unveiling the Inflammatory Messengers After Intracerebral Hemorrhage: The Crosstalk Between Peripheral NETs and Microglia
Provisionally accepted
- 1Changchun University of Chinese Medicine, Changchun, China
- 2Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
- 3Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
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Intracerebral hemorrhage (ICH), a common neurological disorder with a high rate of disability, involves complex immunoinflammatory mechanisms, particularly those related to secondary inflammatory injury. Neutrophils, as the earliest subtype of leukocytes recruited after stroke, play a pivotal role in secondary brain injury. Traditionally, neutrophils were thought to mediate tissue damage primarily via phagocytosis, chemotaxis, and degranulation. However, recent studies have shown that neutrophils also contribute to the pathogenesis of intracerebral hemorrhage by releasing neutrophil extracellular traps (NETs), which exacerbate blood-brain barrier disruption, amplify local inflammation, and promote neuronal injury. This review systematically examines the interactions between the central and peripheral immune systems following ICH. It focuses on the bidirectional regulatory relationship between microglia and neutrophils, and their coordinated roles in inflammation, blood-brain barrier disruption, neurological dysfunction, and cognitive impairment. In addition, this review summarizes recent potential therapeutic strategies targeting the formation and clearance of NETs, including peptidylarginine deiminase 4 inhibitors, reactive oxygen species inhibitors, histone inhibitors, and DNases. These interventions may offer theoretical insights into novel therapeutic targets for mitigating secondary injury following ICH.
Keywords: intracerebral hemorrhage, neutrophil extracellular traps, Microglia, Central and peripheral immune systems, Mechanism analysis
Received: 09 Jun 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Zhang, Jin, Jiang, Zhang, Wu, Xu, Cui, Zhang and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Dongmei Zhang, Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
Jing Lu, Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
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