Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA.
Curr Neuropharmacol. 2009 Sep;7(3):217-27. doi: 10.2174/157015909789152209.
Stroke is a leading cause of morbidity and mortality in the United States. Despite intensive research into the development of treatments that lessen the severity of cerebrovascular injury, no major therapies exist. Though the potential use of adenosine as a neuroprotective agent in the context of stroke has long been realized, there are currently no adenosine-based therapies for the treatment of cerebral ischemia and reperfusion. One of the major obstacles to developing adenosine-based therapies for the treatment of stroke is the prevalence of functional adenosine receptors outside the central nervous system. The activities of peripheral immune and vascular endothelial cells are particularly vulnerable to modulation via adenosine receptors. Many of the pathophysiological processes in stroke are a direct result of peripheral immune infiltration into the brain. Ischemic preconditioning, which can be induced by a number of stimuli, has emerged as a promising area of focus in the development of stroke therapeutics. Reprogramming of the brain and immune responses to adenosine signaling may be an underlying principle of tolerance to cerebral ischemia. Insight into the role of adenosine in various preconditioning paradigms may lead to new uses for adenosine as both an acute and prophylactic neuroprotectant.
中风是美国发病率和死亡率的主要原因。尽管对减轻脑血管损伤严重程度的治疗方法进行了深入研究，但目前仍没有主要的治疗方法。尽管长期以来人们一直认识到腺苷作为中风情况下神经保护剂的潜在用途，但目前尚无基于腺苷的治疗脑缺血和再灌注的方法。开发用于治疗中风的基于腺苷的治疗方法的主要障碍之一是中枢神经系统外功能性腺苷受体的普遍存在。外周免疫和血管内皮细胞的活性特别容易受到腺苷受体的调节。中风中的许多病理生理过程都是外周免疫细胞浸润到大脑的直接结果。缺血预处理可以通过多种刺激诱导，已成为中风治疗发展的一个有前途的重点领域。对大脑和对腺苷信号的免疫反应的重新编程可能是对脑缺血耐受的潜在原则。深入了解腺苷在各种预处理范例中的作用可能会导致将腺苷用作急性和预防性神经保护剂的新用途。
