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Iron-Induced Hydrocephalus: the Role of Choroid Plexus Stromal Macrophages

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Abstract

Evidence indicates that erythrocyte-derived iron and inflammation both play a role in intraventricular hemorrhage-induced brain injury including hydrocephalus. Many immune-associated cells, primarily stromal macrophages, reside at the choroid plexus where they are involved in inflammatory responses and antigen presentation. However, whether intraventricular iron impacts those stromal cells is unknown. The aim of this study was to evaluate the relationship between choroid plexus stromal macrophages and iron-induced hydrocephalus in rats and the impact of minocycline and clodronate liposomes on those changes. Aged (18-month-old) and young (3-month-old) male Fischer 344 rats were used to study choroid plexus stromal macrophages. Rats underwent intraventricular iron injection to induce hydrocephalus and treated with either minocycline, a microglia/macrophage inhibitor, or clodronate liposomes, a macrophage depleting agent. Ventricular volume was measured using magnetic resonance imaging, and stromal macrophages were quantified by immunofluorescence staining. We found that stromal macrophages accounted for about 10% of the total choroid plexus cells with more in aged rats. In both aged and young rats, intraventricular iron injection resulted in hydrocephalus and increased stromal macrophage number. Minocycline or clodronate liposomes ameliorated iron-induced hydrocephalus and the increase in stromal macrophages. In conclusion, stromal macrophages account for ~10% of all choroid plexus cells, with more in aged rats. Treatments targeting macrophages (minocycline and clodronate liposomes) are associated with reduced iron-induced hydrocephalus.

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Funding

Y.H., R.F.K., and G.X. were supported by grants NS-096917, NS-106746, NS-112394, and NS-116786. SK was supported by NS-007222 from the National Institutes of Health.

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Correspondence to Guohua Xi.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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Chaoyi Bian, Yingfeng Wan, Sravanthi Koduri, Ya Hua, Richard F. Keep, and Guohua Xi declare no conflict of interests. Guohua Xi is Deputy Editor-in-Chief of Translational Stroke Research.

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Bian, C., Wan, Y., Koduri, S. et al. Iron-Induced Hydrocephalus: the Role of Choroid Plexus Stromal Macrophages. Transl. Stroke Res. 14, 238–249 (2023). https://doi.org/10.1007/s12975-022-01031-6

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