Amar Arun Paul, Griffin John H, Zlokovic Berislav V
Department of Neurosurgery, Keck School of Medicine of the University of Southern California, University of Southern California Los Angeles, CA, USA.
Department of Molecular and Experimental Medicine, Scripps Research Institute La Jolla, CA, USA ; Department of Medicine, Division of Hematology/Oncology, University of California, San Diego San Diego, CA, USA.
Front Cell Neurosci. 2015 Sep 2;9:344. doi: 10.3389/fncel.2015.00344. eCollection 2015.
In the treatment of acute ischemic stroke (AIS), vessel recanalization correlates with improved functional status and reduced mortality. Mechanical neurothrombectomy achieves a higher likelihood of revascularization than intravenous thrombolysis (IVT), but there remains significant discrepancy between rates of recanalization and rates of favorable outcome. The poor neurological recovery among some stroke patients despite successful recanalization confirms the need for adjuvant therapy, such as pharmacological neuroprotection. Prior clinical trials of neuroprotectant drugs failed perhaps due to inability of the agent to reach the ischemic tissue beyond the occluded artery. A protocol that couples mechanical neurothrombectomy with concurrent delivery of a neuroprotectant overcomes this pitfall. Activated protein C (APC) exerts pleiotropic anti-inflammatory, anti-apoptotic, antithrombotic, cytoprotective, and neuroregenerative effects in stroke and appears a compelling candidate for this novel approach.
在急性缺血性卒中(AIS)的治疗中,血管再通与功能状态改善及死亡率降低相关。与静脉溶栓(IVT)相比,机械取栓术实现血管再通的可能性更高,但再通率与良好预后率之间仍存在显著差异。尽管成功实现了再通,但部分卒中患者的神经功能恢复不佳,这证实了辅助治疗(如药理学神经保护)的必要性。先前的神经保护药物临床试验可能因药物无法到达闭塞动脉以外的缺血组织而失败。将机械取栓术与同时递送神经保护剂相结合的方案克服了这一缺陷。活化蛋白C(APC)在卒中中发挥多效性抗炎、抗凋亡、抗血栓形成、细胞保护和神经再生作用,似乎是这种新方法的有力候选药物。