Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital. 123 Dapi Road, Kaohsiung, 83301, Taiwan.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital. 123 Dapi Road, Kaohsiung, 83301, Taiwan; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital. 123 Dapi Road, Kaohsiung 83301, Taiwan.
Life Sci. 2019 Nov 1;236:116889. doi: 10.1016/j.lfs.2019.116889. Epub 2019 Oct 11.
Stroke is the major cause of adult disability and the second or third leading cause of death in developed countries. The treatment options for stroke (thrombolysis or thrombectomy) are restricted to a small subset of patients with acute ischemic stroke because of the limited time for an efficacious response and the strict criteria applied to minimize the risk of cerebral hemorrhage. Attempts to develop new treatments, such as neuroprotectants, for acute ischemic stroke have been costly and time-consuming and to date have yielded disappointing results. The repurposing approved drugs known to be relatively safe, such as statins and minocycline, may provide a less costly and more rapid alternative to new drug discovery in this clinical condition. Because adequate perfusion is thought to be vital for a neuroprotectant to be effective, endovascular thrombectomy (EVT) with advanced imaging modalities offers the possibility of documenting reperfusion in occluded large cerebral vessels. An examination of established medications that possess neuroprotective characters using in a large-vessel occlusive disorder with EVT may speed the identification of new and more broadly efficacious medications for the treatment of ischemic stroke. These approaches are highlighted in this review along with a critical assessment of drug repurposing combined with reperfusion therapy as a supplementary means for halting or mitigating stroke-induced brain damage.
中风是成年人残疾的主要原因,也是发达国家第二或第三大致死原因。中风的治疗选择(溶栓或血栓切除术)仅限于少数急性缺血性中风患者,因为有效的反应时间有限,并且为了最大限度地降低脑出血的风险,适用严格的标准。为急性缺血性中风开发新的治疗方法(如神经保护剂)既昂贵又耗时,迄今为止,结果令人失望。重新利用已批准的、已知相对安全的药物(如他汀类药物和米诺环素)可能为这种临床情况的新药发现提供一种成本更低、速度更快的替代方案。由于人们认为充分灌注对于神经保护剂的有效性至关重要,因此使用先进的血管内血栓切除术(EVT)和成像方式有可能证明闭塞性大脑大血管的再灌注。使用 EVT 检查具有神经保护作用的已确立药物,可以加速识别治疗缺血性中风的新的、更广泛有效的药物。这些方法在本文中得到了强调,并对药物再利用与再灌注治疗相结合作为阻止或减轻中风引起的脑损伤的辅助手段进行了批判性评估。