Iron Overload Exacerbates the Risk of Hemorrhagic Transformation After tPA (Tissue-Type Plasminogen Activator) Administration in Thromboembolic Stroke Mice

Stroke; a Journal of Cerebral Circulation
Isaac García-YébenesIgnacio Lizasoain

Abstract

Background and Purpose- Recanalization with tPA (tissue-type plasminogen activator) is the only pharmacological therapy available for patients with ischemic stroke. However, the percentage of patients who may receive this therapy is limited by the risk of hemorrhagic transformation (HT)-the main complication of ischemic stroke. Our aim is to establish whether iron overload affects HT risk, to identify mechanisms that could help to select patients and to prevent this devastating complication. Methods- Mice fed with control or high-iron diet were subjected to thromboembolic stroke, with or without tPA therapy at different times after occlusion. Blood samples were collected for determination of malondialdehyde, matrix metalloproteinases, and fibronectin. Brain samples were collected 24 hours after occlusion to determine brain infarct and edema size, hemorrhage extension, IgG extravasation, and inflammatory and oxidative markers (neutrophil infiltration, 4-hydroxynonenal, and matrix metalloproteinase-9 staining). Results- Despite an increased rate of recanalization, iron-overload mice showed less neuroprotection after tPA administration. Importantly, iron overload exacerbated the risk of HT after early tPA administration, accelerat...Continue Reading

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Citations

Nov 23, 2019·CNS Neuroscience & Therapeutics·Yan LiPei-Ying Li
Jun 14, 2019·The Journal of International Medical Research·Snezana Ciric ZdravkovicDragana Stanojevic
Dec 27, 2019·Current Opinion in Anaesthesiology·Thomas B BartnikasCaroline A Enns
Nov 3, 2020·Frontiers in Cellular Neuroscience·Jie LiuYi Yang
Jun 24, 2020·Mitochondrion·Jumana SalehMarvin Edeas
Jul 15, 2021·Oxidative Medicine and Cellular Longevity·Yue ZhouJinwen Ge
Sep 24, 2021·Journal of Neurochemistry·Md JakariaScott Ayton

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