Dietary Iron Restriction Protects against Aneurysm Rupture in a Mouse Model of Intracranial Aneurysm

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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 (<i>n</i> = 23) or a normal diet (<i>n</i> = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination. <b><i>Results:</i></b> The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; <i>p</i> < 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 (<i>p</i> < 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 mouse aneurysms. <b><i>Conclusions:</i></b> These findings suggest that iron is involved in intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture.

Current understanding of macrophages in intracranial aneurysm: relevant etiological manifestations, signaling modulation and therapeutic strategies

“…The MSR1 named CD204, was primarily found on the various types of macrophage surface and was responsible for the pro-inflammatory polarization both in vivo and in vitro ( 37 , 38 ). In the aspect of nutrition improvement, recent studies demonstrated that iron limitation and coenzyme Q10 (CoQ10) administration significantly ameliorated the macrophages infiltration and oxidative stress, thereby attenuating IA progression and rupture ( 39 , 40 ). Through engulfed ultrasmall superparamagnetic iron oxide particle, the macrophages enrichment vessel wall imaging in IA has potential in qualitative evaluation and can be used to evaluate the efficacy of medication ( 41 ).…”