biostudies-literatureLi YGeneral Program of the China Postdoctoral Science FoundationWV-INBREGeneral Program of the Heilongjiang Provincial Postdoctoral Science FoundationYoung Talents Program of the First Affiliated Hospital of Harbin Medical UniversityNatural Science Foundation of Heilongjiang ProvinceWV-CTSINIGMS NIH HHS119https://www.ebi.ac.uk/biostudies/studies/S-EPMC12870926biostudies-literatureUnknown24(1)Subarachnoid hemorrhage (SAH) is a devastating stroke subtype often leading to poor neurological outcomes. Iron homeostasis imbalance is a key contributor to cognitive dysfunction in neurological diseases. Extracellular vesicles, including exosomes (EXs), are crucial mediators of intercellular communication. This study investigated the role of EXs in post-SAH iron metabolism and neurological impairment. We isolated EXs from various neural cells (microglia, astrocytes, endothelial cells, neurons; n = 4-6 independent isolations) in vitro after SAH mimicked by oxyhemoglobin (OxyHb) or hemin. We found that microglial EXs (MC-EXs) were significantly enriched in iron and potently impaired neuronal viability. Using specific inhibitors and fluorescence imaging, we demonstrated that neurons internaJournal of nanobiotechnologyMicroglia-derived iron-overloaded exosomes induce neuronal ferroptosis and aggravate neurological impairment after subarachnoid hemorrhage.PMC12870926YQ2023H0082021Y10P20GM1034342021MD703829P20 GM103434U54GM104942LBH-Z20169PL2024H055U54 GM104942Meng FLi XLi YYao ZChen JSun BWang XAWu PHuang LBihl JShi HSawant HfalseMicroglia-derived iron-overloaded exosomes induce neuronal ferroptosis and aggravate neurological impairment after subarachnoid hemorrhage.Subarachnoid hemorrhage (SAH) is a devastating stroke subtype often leading to poor neurological outcomes. Iron homeostasis imbalance is a key contributor to cognitive dysfunction in neurological diseases. Extracellular vesicles, including exosomes (EXs), are crucial mediators of intercellular communication. This study investigated the role of EXs in post-SAH iron metabolism and neurological impairment. We isolated EXs from various neural cells (microglia, astrocytes, endothelial cells, neurons; n = 4-6 independent isolations) in vitro after SAH mimicked by oxyhemoglobin (OxyHb) or hemin. We found that microglial EXs (MC-EXs) were significantly enriched in iron and potently impaired neuronal viability. Using specific inhibitors and fluorescence imaging, we demonstrated that neurons interna2026-01-01T00:00:00Z2026 Jan2026-07-15T06:11:28.451Z2026-06-30T03:16:19.766ZS-EPMC128709264150801810.1186/s12951-025-03974-y