Iron chelation suppresses secondary bleeding after intracerebral hemorrhage in angiotensin II-infused mice

Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE

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.

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.