INTRODUCTION Iron accumulation in vessel walls induces oxidative stress and inflammation, which can cause cerebrovascular damage, vascular wall degeneration, and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture. METHODS Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet (n = 23) or a normal diet (n = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination. RESULTS The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; p < 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2'-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p < 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2'-deoxyguanosine in both normal diet and iron-restricted diet mice aneurysms. CONCLUSIONS These findings suggest that iron is involved intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture.

中文翻译：

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饮食铁限制可防止颅内动脉瘤小鼠模型中的动脉瘤破裂。

引言血管壁中铁的积累会引起氧化应激和炎症，从而导致脑血管损伤、血管壁变性以及颅内动脉瘤形成、生长和破裂。颅内动脉瘤破裂引起的蛛网膜下腔出血导致显着的发病率和死亡率。本研究使用颅内动脉瘤小鼠模型来评估饮食铁限制对动脉瘤形成和破裂的影响。方法采用醋酸脱氧皮质酮盐诱导的高血压和向基底池脑脊液中单次注射弹性蛋白酶来诱导颅内动脉瘤。小鼠被喂食铁限制饮食（n = 23）或正常饮食（n = 25）。通过神经症状发现动脉瘤破裂，通过尸检证实颅内动脉瘤伴蛛网膜下腔出血。结果 与正常饮食小鼠（76%；p < 0.05）相比，限铁饮食小鼠的动脉瘤破裂率（37%）显着降低。铁限制饮食小鼠的血清氧化应激、铁积累、巨噬细胞浸润和血管壁中的 8-羟基-2'-脱氧鸟苷较低（p < 0.01）。在正常饮食和铁限制饮食小鼠动脉瘤中，铁阳性面积与CD68阳性和8-羟基-2'-脱氧鸟苷的面积相似。结论 这些发现表明，铁通过血管炎症和氧化应激参与颅内动脉瘤破裂。饮食铁限制可能在预防颅内动脉瘤破裂方面发挥重要作用。