Iron chelation suppresses secondary bleeding after intracerebral hemorrhage in angiotensin II-infused mice.
Iron chelation suppresses secondary bleeding after intracerebral hemorrhage in angiotensin II-infused mice.
复制标题
铁螯合抑制血管紧张素II灌注小鼠脑出血后的继发性出血。
DOI：
10.1111/cns.13706
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发表时间：
2021-11
影响因子：
5.5
通讯作者：
Feng H
中科院分区：
文献类型：
--
作者：
Wang J;Tang XQ;Xia M;Li CC;Guo C;Ge HF;Yin Y;Wang B;Chen WX;Feng H
脑出血（ICH）后继发出血和进一步血肿扩大（HE）加重脑损伤。大部分HE由高血压ICH引起。先前的研究报告高血压患者大脑中的铁含量较高。铁超负荷加重血栓栓塞性中风小鼠出血性转化的风险。高血压过程中的铁超载是否参与高血压脑出血的继发性出血尚不清楚。通过渗透泵持续输注血管紧张素II（Ang II）到C57 BL/6小鼠中来诱导高血压。通过纹状体内注射液体聚合物Onyx-18模拟ICH。通过甲磺酸去铁胺或右旋糖酐铁注射液实现铁螯合和铁过载。通过测量同侧大脑半球中的血红蛋白含量来量化继发性出血。Ang II诱导的高血压小鼠在ICH建模后显示脑内铁积累增加和继发性出血扩大。此外，铁螯合抑制，而铁过载加重继发性出血。从机制上讲，铁加剧了收缩性脑血管平滑肌细胞（VSMC）的丧失，加重了Ang II诱导的高血压小鼠的血脑屏障（BBB）渗漏，并增加了ICH后的胶质细胞和MMP 9蓄积。铁超载在Ang II诱导的高血压小鼠ICH后继发性出血中起关键作用。Ang II诱导的高血压过程中的铁螯合抑制ICH后的继发性出血Ang II诱导的高血压小鼠脑组织中的铁蓄积可能加剧收缩性VSMC的丧失，增强血管周围炎症和BBB渗漏。这些因素可能导致血管脆性增加和破裂脆弱性增加，最终导致更多继发性出血和ICH后的HE。
Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE results from hypertensive ICH. Previous study reported higher iron content in the brains of hypertensive patients. Iron overload exacerbates the risk of hemorrhagic transformation in thromboembolic stroke mice. Whether iron overload during the process of hypertension participates in secondary bleeding of hypertensive ICH remains unclear. Hypertension was induced by continuous infusion of angiotensin II (Ang II) with an osmotic pump into C57BL/6 mice. ICH was simulated by intrastriatal injection of the liquid polymer Onyx‐18. Iron chelation and iron overload was achieved by deferoxamine mesylate or iron dextran injection. Secondary bleeding was quantified by measuring the hemoglobin content in the ipsilateral brain hemisphere. Ang II‐induced hypertensive mice showed increased iron accumulation in the brain and expanded secondary hemorrhage after ICH modeling. Moreover, iron chelation suppressed while iron overload aggravated secondary bleeding. Mechanistically, iron exacerbated the loss of contractile cerebral vascular smooth muscle cells (VSMCs), aggravated blood–brain barrier (BBB) leakage in Ang II‐induced hypertensive mice, and increased glial and MMP9 accumulation after ICH. Iron overload plays a key role in secondary bleeding after ICH in Ang II‐induced hypertensive mice. Iron chelation during the process of Ang II‐induced hypertension suppresses secondary bleeding after ICH. Iron accumulation in the brain tissues of Ang II‐induced hypertensive mice might exacerbate the loss of contractile VSMCs, enhance perivascular inflammation and BBB leakage. These factors might lead to increased vascular fragility and increased vulnerability to rupture, ultimately causing more secondary bleeding and subsequent HE after ICH.
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影响因子：
5.5
作者：
Li, Cheng-Cheng;Chen, Wei-Xiang;Feng, Hua
通讯作者：
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通讯作者：
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作者：
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通讯作者：
dos Santos, Leonardo
影响因子：
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作者：
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通讯作者：
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