Turner Ryan C, Lucke-Wold Brandon, Lucke-Wold Noelle, Elliott Alisa S, Logsdon Aric F, Rosen Charles L, Huber Jason D
Department of Neurosurgery, One Medical Center Drive, West Virginia University School of Medicine, P.O. Box 9183, Morgantown, WV 26506, USA.
Int J Mol Sci. 2013 Jan 17;14(1):1890-917. doi: 10.3390/ijms14011890.
The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics.
自组织型纤溶酶原激活剂（tPA）问世以来，缺血性中风神经保护剂从实验室到临床的转化在很大程度上未能产生更好的治疗方法。转化失败的一个可能原因是未能认识到中风的最大风险因素——年龄，以及其他与中风相关的常见合并症，如高血压、肥胖和糖尿病。在本综述中，我们强调了研究这些因素的机制以及已涉及因素的研究结果。我们还讨论了其他与中风风险增加相关的生活方式因素的潜在作用，如睡眠片段化和/或睡眠剥夺。此外，尽管有数据表明缺血性中风后患者就诊延迟，但许多提出的治疗药物仍针对缺血发作后不久发生的分子机制。调节炎症已被确定为一条有前景的治疗途径，这与诸如米诺环素等抗炎化合物正在进行的临床试验的初步成功相一致。我们综述了炎症在中风中的作用，特别是炎症细胞募集和巨噬细胞表型在炎症过程中的作用。新出现的证据表明神经免疫相互作用的作用日益增加，这导致人们对识别指示神经损伤的外周生物标志物的兴趣增加。我们希望，对影响中风病理生理学因素的识别和研究可能会带来更好的治疗方法。
