This review systematically summarizes the research progress on peripheral inflammation in spontaneous intracerebral hemorrhage (ICH), focusing on the interaction mechanisms of the “peripheral-central inflammation axis,” key biomarkers, and their clinical translational potential. After ICH, hematoma components (such as hemoglobin and thrombin) and damage-associated molecular patterns (DAMPs) disrupt the blood–brain barrier, activating peripheral immune cells (neutrophils, monocytes/macrophages, T cells, etc.) to migrate to the central nervous system, forming a “peripheral inflammation-central inflammation” positive feedback loop that exacerbates brain edema, hematoma expansion, and neurological deficits. Peripheral inflammatory cells mediate secondary damage by secreting pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and reactive oxygen species (ROS), while certain subpopulations (e.g., M2 macrophages, N2 neutrophils) participate in tissue repair. This article further summarizes the research progress on peripheral inflammation-related biomarkers in ICH, covering soluble serum factors (IL-6, IL-31, TNF-α, HMGB1, mCRP, etc.), acute-phase proteins (PCT, C3, C1q), and cell count ratios (NLR, PWR, SIRI), and highlights the potential application of single-cell sequencing technology in analyzing immune cell heterogeneity and dynamic evolution. In terms of interventions, this article reviews the efficacy and limitations of traditional anti-inflammatory drugs (NSAIDs, corticosteroids) and targeted inflammatory pathways (IL-1R antagonists, HMGB1 inhibitors, LPA1 antagonists, IL-4) in animal experiments and early clinical studies, and explores the potential value of non-pharmacological strategies such as the “gut-brain axis” and splenectomy. Future research should focus on elucidating the “peripheral-central” interaction mechanisms, multi-center biomarker validation, and the development of personalized anti-inflammatory intervention strategies to advance the clinical translation of ICH precision diagnosis and treatment.

Funding: This work was supported by the National Natural Science Foundation of China (81960221 to X.P.Y., 82,260,249 to X.P.Y.), Jiangxi Provincial Health Commission Science and Technology Plan project (202311506 to Z.Y.C.), Jiangxi Provincial Administration of Traditional Chinese Medicine science and technology plan project (2022A322 to Z.Y.C.), Jiangxi Provincial Natural Science Foundation Grant (20212BAB216069 to L.H.), Research and Reform Project on Education and Teaching in Ordinary Colleges and Universities of Jiangxi Province (JXJG-24-17-20 to Z.Y.C., JXYJG-2024-140 to X.P.Y.).

The classification and mechanism of perihematomal edema in cerebral hemorrhage are complicated. The edema theory in different periods needs to be unified due to various reasons. Secondary perihematomal edema is the most important cause of “secondary brain injury”. Early intervention to inhibit the occurrence of perihematomal edema is important for the progression of the disease and long-term prognosis. From the basic and clinical perspectives, this paper analyzes the classification and staging characteristics and mechanism of perihematomal edema, and proposes that cerebrospinal fluid is a non-negligible cause of hyperearly perihematomal edema.