Otsu Yutaka, Namekawa Masaki, Toriyabe Masafumi, Ninomiya Itaru, Hatakeyama Masahiro, Uemura Masahiro, Onodera Osamu, Shimohata Takayoshi, Kanazawa Masato
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan; Department of Medical Technology, Graduate School of Health Sciences, Niigata University, Niigata, Japan.
J Neurol Sci. 2020 Dec 15;419:117217. doi: 10.1016/j.jns.2020.117217. Epub 2020 Nov 4.
Reperfusion therapies by tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) have ushered in a new era in the treatment of acute ischemic stroke (AIS). However, reperfusion therapy-related HT remains an enigma.
To provide a comprehensive review focused on emerging concepts of stroke and therapeutic strategies, including the use of protective agents to prevent HT after reperfusion therapies for AIS.
A literature review was performed using PubMed and the ClinicalTrials.gov database.
Risk of HT increases with delayed initiation of tPA treatment, higher baseline glucose level, age, stroke severity, episode of transient ischemic attack within 7 days of stroke onset, and hypertension. At a molecular level, HT that develops after thrombolysis is thought to be caused by reactive oxygen species, inflammation, remodeling factor-mediated effects, and tPA toxicity. Modulation of these pathophysiological mechanisms could be a therapeutic strategy to prevent HT after tPA treatment. Clinical mechanisms underlying HT after MT are thought to involve smoking, a low Alberta Stroke Program Early CT Score, use of general anesthesia, unfavorable collaterals, and thromboembolic migration. However, the molecular mechanisms are yet to be fully investigated. Clinical trials with MT and protective agents have also been planned and good outcomes are expected.
To fully utilize the easily accessible drug-tPA-and the high recanalization rate of MT, it is important to reduce bleeding complications after recanalization. A future study direction could be to investigate the recovery of neurological function by combining reperfusion therapies with cell therapies and/or use of pleiotropic protective agents.
组织型纤溶酶原激活剂（tPA）和机械取栓术（MT）的再灌注治疗开启了急性缺血性卒中（AIS）治疗的新时代。然而，与再灌注治疗相关的颅内出血（HT）仍然是一个谜。
提供一篇全面综述，重点关注卒中的新观念和治疗策略，包括使用保护剂预防AIS再灌注治疗后的HT。
使用PubMed和ClinicalTrials.gov数据库进行文献综述。
HT的风险随着tPA治疗开始延迟、基线血糖水平升高、年龄、卒中严重程度、卒中发作7天内短暂性脑缺血发作、高血压而增加。在分子水平上，溶栓后发生的HT被认为是由活性氧、炎症、重塑因子介导的效应和tPA毒性引起的。调节这些病理生理机制可能是预防tPA治疗后HT的一种治疗策略。MT后HT的临床机制被认为涉及吸烟、低阿尔伯塔卒中项目早期CT评分、全身麻醉的使用、侧支循环不良和血栓栓塞迁移。然而，分子机制尚未得到充分研究。MT和保护剂的临床试验也已计划，预计会有良好结果。
为了充分利用易于获得的药物tPA和MT的高再通率，降低再通后的出血并发症很重要。未来的研究方向可能是研究将再灌注治疗与细胞治疗和/或使用多效保护剂相结合对神经功能恢复的影响。
