Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke
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REVIEW PAPER
Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke Chengli Liu1 · Jie Xie1 · Shanshan Sun2 · Hui Li1 · Tianyu Li1 · Chao Jiang3 · Xuemei Chen4 · Junmin Wang4 · Anh Le5 · Jiarui Wang6 · Zhanfei Li1 · Jian Wang4 · Wei Wang1 Received: 25 June 2020 / Accepted: 22 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Hemorrhagic transformation (HT) is a common complication after thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in ischemic stroke. In this article, recent research progress of HT in vivo and in vitro studies was reviewed. We have discussed new potential mechanisms and possible experimental models of HT development, as well as possible biomarkers and treatment methods. Meanwhile, we compared and analyzed rodent models, large animal models and in vitro BBB models of HT, and the limitations of these models were discussed. The molecular mechanism of HT was investigated in terms of BBB disruption, rt-PA neurotoxicity and the effect of neuroinflammation, matrix metalloproteinases, reactive oxygen species. The clinical features to predict HT were represented including blood biomarkers and clinical factors. Recent progress in neuroprotective strategies to improve HT after stroke treated with rt-PA is outlined. Further efforts need to be made to reduce the risk of HT after rt-PA therapy and improve the clinical prognosis of patients with ischemic stroke. Keywords Tissue plasminogen activator · Ischemic stroke · Hemorrhagic transformation · Blood · Brain barrier
Introduction
Chengli Liu and Jie Xie have contributed equally to this work. * Jian Wang [email protected] * Wei Wang [email protected] 1
Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China
2
Department of Ultrasound Imaging, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China
3
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China
4
Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Henan 450000, People’s Republic of China
5
Washington University in St. Louis, Saint Louis, MO 63130, USA
6
The Johns Hopkins University, Baltimore, MD 21218, USA
Stroke including ischemic stroke and intracerebral hemorrhage, is the primary cause of disability, producing immense health and economic burdens in adults worldwide, and affects approximately 795,000 people annually (Benjamin et al. 2017). Ischemic stroke occurs when blood flowing to a part of the brain is temporarily or permanently restricted, which results in irreversible damage to the ischemic core and surrounding areas of possible recoverable tissue (Lv et al. 2018). Some studies estimated that more than 80% of strokes are ischemic brain injury caused by thrombi and
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