期刊
CNS NEUROSCIENCE & THERAPEUTICS
卷 27, 期 11, 页码 1327-1338出版社
WILEY
DOI: 10.1111/cns.13706
关键词
angiotensin II; cerebral vascular injury; intracerebral hemorrhage; iron overload; secondary bleeding
资金
- National Natural Science Foundation of China [82001263, 2014CB541606, 82030036]
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.
Aims 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. Methods 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. Results 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. Conclusion 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.
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