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.
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Acknowledgements
We thank Jian Wang, Zhanfei Li, Anh Le and Jiarui Wang for assistance with the manuscript preparation.
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This article was supported by grants from the National Natural Science Foundation of China (81801174 to W.W., 81571891 to Z.F.L.).
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by CL, JX, SS, HL, TL, CJ, XC, JW, AL, JW and ZL. The first draft of the manuscript was written by CL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Liu, C., Xie, J., Sun, S. et al. Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke. Cell Mol Neurobiol 42, 621–646 (2022). https://doi.org/10.1007/s10571-020-00985-1
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DOI: https://doi.org/10.1007/s10571-020-00985-1