Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke
Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke
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DOI：
10.3171/2017.1.focus16522
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发表时间：
2017-04-01
影响因子：
4.1
通讯作者：
Park, Min S.
中科院分区：
文献类型：
--
作者：
Karsy, Michael;Brock, Andrea;Park, Min S.
中风是美国残疾的主要原因。虽然在内科和外科溶栓技术领域取得了重大进展，但预防继发性脑损伤和尽量减少残疾的神经保护剂仍然有限。在评价各种化合物的临床前和临床试验中，仅报告了有限的成功。在这篇综述中，作者讨论了最新的信息有关的基础分子生物学中风以及战略，旨在减轻这种复杂的信号级联。涉及N-甲基-d-天冬氨酸和a-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体拮抗剂、氯美噻唑、抗氧化剂、胞磷胆碱、一氧化氮和免疫调节剂的历史研究试验结果为当前的进展奠定了基础。此外，最近涉及治疗性低温、镁、白蛋白、格列本脲、尿酸和各种其他治疗的研究提供了更多选择。神经保护剂与现有的溶栓治疗联合使用可能是许多令人兴奋的进一步发展领域之一。虽然过去的缺血性卒中的神经保护剂的试验是有限的，中风的机制，动物模型和试验设计的重要见解，逐步改善未来的治疗方法。
Stroke is a leading cause of disability in the US. Although there has been significant progress in the area of medical and surgical thrombolytic technologies, neuroprotective agents to prevent secondary cerebral injury and to minimize disability remain limited. Only limited success has been reported in preclinical and clinical trials evaluating a variety of compounds. In this review, the authors discuss the most up-to-date information regarding the underlying molecular biology of stroke as well as strategies that aim to mitigate this complex signaling cascade. Results of historical research trials involving N-methyl-d-aspartate and a-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonists, clomethiazole, antioxidants, citicoline, nitric oxide, and immune regulators have laid the groundwork for current progress. In addition, more recent studies involving therapeutic hypothermia, magnesium, albumin, glyburide, uric acid, and a variety of other treatments have provided more options. The use of neuroprotective agents in combination or with existing thrombolytic treatments may be one of many exciting areas of further development. Although past trials of neuroprotective agents in ischemic stroke have been limited, significant insights into mechanisms of stroke, animal models, and trial design have incrementally improved approaches for future therapies.