Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Department of Ultrasound Imaging, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Cell Mol Neurobiol. 2022 Apr;42(3):621-646. doi: 10.1007/s10571-020-00985-1. Epub 2020 Oct 30.
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.
出血性转化（HT）是缺血性脑卒中患者接受重组组织型纤溶酶原激活剂（rt-PA）溶栓后常见的并发症。本文综述了 HT 的体内和体外研究的最新进展。我们讨论了 HT 发展的新的潜在机制和可能的实验模型，以及可能的生物标志物和治疗方法。同时，我们比较和分析了 HT 的啮齿动物模型、大动物模型和体外 BBB 模型，并讨论了这些模型的局限性。从 BBB 破坏、rt-PA 神经毒性以及神经炎症、基质金属蛋白酶、活性氧的影响等方面探讨了 HT 的分子机制。还介绍了包括血液生物标志物和临床因素在内的预测 HT 的临床特征。概述了 rt-PA 治疗后改善 HT 的神经保护策略的最新进展。需要进一步努力降低 rt-PA 治疗后 HT 的风险，改善缺血性脑卒中患者的临床预后。
