Fatty acid-binding protein 4 drives microglia-mediated neuroinflammation through promoting S100A9 expression and lipid droplet accumulation after intracerebral hemorrhage

作者：Jiaqing He, Zijuan Qin, Haixiao Liu, Yaning Cai, Hao Wu, Tinghao Wang, Qing Hu, Yanni Xu, Pan Yang, Xun Wu, Yan Qu, Wei Guo · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03573-6 · 被引用次数：10 · 研究领域：Intracerebral and Subarachnoid Hemorrhage Research、S100 Proteins and Annexins、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND: As primary immune sentinels of the central nervous system (CNS), microglia respond rapidly to acute brain injury and engage in dynamic crosstalk with infiltrating peripheral immune cells. This interplay critically shapes the neuroinflammatory microenvironment-a key determinant of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). Fatty acid-binding protein 4 (FABP4), an adipokine associated with metabolic disorders, is recognized as a pivotal modulator of inflammatory responses; however, its role in ICH-induced SBI remains undefined. OBJECTIVES: To investigate the pathogenic functions of FABP4 in microglia after ICH, elucidate its molecular mechanisms, and develop targeted therapeutic strategies. METHODS: Blood and brain tissue samples from ICH patients were analyzed to evaluate the relationships between FABP4 expression and prognosis. Behavioral tests, Nissl staining, and Golgi-Cox staining were used to quantify neuronal damage. Immunofluorescence and flow cytometry were used to assess microglial activation and immune cell infiltration. Transcriptomic, proteomic, co-immunoprecipitation, western blotting, and ChIP‒qPCR analyses were used to examine the FABP4 regulatory network. Brain-targeted nanoparticles were engineered to deliver FABP4-specific siRNA. RESULTS: Clinical analyses revealed microglia-specific FABP4 upregulation in ICH patients, correlating with poor neurological outcomes. Microglial Fabp4 knockout in mice attenuated neuronal los...