Reactive astrocyte-derived exosomes enhance intracranial lymphatic drainage in mice after intracranial hemorrhage

作者：Kexin Li, Yuheng Liu, Junjie Gong, Jing Li, Mingyu Zhao, Chengyou Hong, Yuchi Zhang, Mengyao He, Zhenye Zhu, Zhijuan Chen, Zengguang Wang · 发表于：Fluids and Barriers of the CNS · 年份：2025 · DOI：10.1186/s12987-025-00651-y · 被引用次数：8 · 研究领域：Intracerebral and Subarachnoid Hemorrhage Research、Cerebrospinal fluid and hydrocephalus、Intracranial Aneurysms: Treatment and Complications

BACKGROUND: After intracranial hemorrhage (ICH), the formation of primary hematoma foci leads to the development of secondary brain injury factors such as perihematomal edema (PHE) and accumulation of toxic metabolites, which severely affect the survival and prognosis of patients. The intracerebral lymphatic system, proposed by Jeffrey J. Iliff et al., plays an important role in central nervous system (CNS) fluid homeostasis and waste removal, while reactive astrocyte-derived exosomes have shown therapeutic potential in CNS disorders. Our study focuses on the effects of hemin-treated reactive astrocyte-derived exosomes on the functional integrity of the glymphatic system (GLS) after ICH and their potential mechanism of action in repairing brain injury. METHODS: Hemin, an iron-rich porphyrin compound, was used to construct the in vitro model of ICH. Primary astrocytes were treated with complete medium supplemented with different concentrations of hemin to obtain exosomes secreted by them, and mice with ICH induced by the collagenase method were intervened by intranasal administration. Solute clearance efficiency was assessed by intracranial injection of cerebrospinal fluid tracers and fluorescent magnetic beads. Immunofluorescence analysis of Aquaporin 4 (AQP4) polarization and astrocyte proliferation. Magnetic Resonance Imaging was used to visualize and quantify the volume of hematoma foci and PHE, and Western Blot was used to analyze the accumulation of toxic metabolites, wh...