Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Department of Neurosurgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
Transl Stroke Res. 2023 Apr;14(2):238-249. doi: 10.1007/s12975-022-01031-6. Epub 2022 May 11.
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.
证据表明，红细胞衍生的铁和炎症均在脑室出血引起的脑损伤中发挥作用，包括脑积水。许多免疫相关细胞，主要是基质巨噬细胞，存在于脉络丛中，参与炎症反应和抗原呈递。然而，脑室中的铁是否会影响这些基质细胞尚不清楚。本研究旨在评估大鼠脉络丛基质巨噬细胞与铁诱导性脑积水之间的关系，以及米诺环素和氯膦酸脂质体对这些变化的影响。使用老年（18 月龄）和年轻（3 月龄）雄性 Fischer 344 大鼠研究脉络丛基质巨噬细胞。大鼠接受脑室铁注射以诱导脑积水，并接受米诺环素（小胶质细胞/巨噬细胞抑制剂）或氯膦酸脂质体（巨噬细胞耗竭剂）治疗。通过磁共振成像测量脑室容积，并通过免疫荧光染色定量基质巨噬细胞。我们发现，基质巨噬细胞占脉络丛总细胞的 10%左右，老年大鼠中更多。在老年和年轻大鼠中，脑室铁注射导致脑积水和基质巨噬细胞数量增加。米诺环素或氯膦酸脂质体改善了铁诱导的脑积水和基质巨噬细胞的增加。总之，基质巨噬细胞占脉络丛总细胞的 10%左右，老年大鼠中更多。针对巨噬细胞的治疗（米诺环素和氯膦酸脂质体）与减少铁诱导的脑积水有关。
