1 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
J Cereb Blood Flow Metab. 2019 Jan;39(1):20-35. doi: 10.1177/0271678X18807309. Epub 2018 Oct 18.
The significant morbidity that accompanies stroke makes it one of the world's most devastating neurological disorders. Currently, proven effective therapies have been limited to thrombolysis and thrombectomy. The window for the administration of these therapies is narrow, hampered by the necessity of rapidly imaging patients. A therapy that could extend this window by protecting neurons may improve outcome. Endogenous neuroprotection has been shown to be, in part, due to changes in mTOR signalling pathways and the instigation of productive autophagy. Inducing this effect pharmacologically could improve clinical outcomes. One such therapy already in use in transplant medicine is the mTOR inhibitor rapamycin. Recent evidence suggests that rapamycin is neuroprotective, not only via neuronal autophagy but also through its broader effects on other cells of the neurovascular unit. This review highlights the potential use of rapamycin as a multimodal therapy, acting on the blood-brain barrier, cerebral blood flow and inflammation, as well as directly on neurons. There is significant potential in applying this old drug in new ways to improve functional outcomes for patients after stroke.
脑卒中伴随的高发病率使其成为世界上最具破坏性的神经疾病之一。目前，已证实有效的治疗方法仅限于溶栓和血栓切除术。这些治疗方法的应用窗口很窄，因为需要快速对患者进行成像。一种通过保护神经元来延长该窗口的治疗方法可能会改善预后。内源性神经保护部分归因于 mTOR 信号通路的变化和自噬的启动。通过药理学诱导这种效应可能会改善临床结果。一种已经在移植医学中使用的此类疗法是 mTOR 抑制剂雷帕霉素。最近的证据表明，雷帕霉素具有神经保护作用，不仅通过神经元自噬，而且还通过其对神经血管单元中其他细胞的更广泛作用。这篇综述强调了雷帕霉素作为一种多模式治疗方法的潜在用途，可作用于血脑屏障、脑血流和炎症，以及直接作用于神经元。以新的方式应用这种旧药物有很大的潜力，可以改善脑卒中患者的功能预后。
