ABSTRACT
Until recently, the main focus of studies of adenosine and its receptors in the context of stroke concentrated on A1 receptors whose stimulation has been consistently shown to result in the reduction of brain damage following experimentally induced global and focal brain ischemia in animals. The promising results of these experiments led many authors to propose the development of therapeutics targeted specifically at A1 receptors and their clinical testing as therapeutics not only against stroke-induced damage but in the context of other neurodegenerative diseases as well. The most recent discoveries indicate that adenosine-mediated actions might be far more complex than originally anticipated, and they may range from purely protective to lethal. The systemic complexity of adenosine-induced effects appears to cast doubts about the rapid development of stroke treatment based on the direct activation of the adenosine receptors, although improving the understanding of these effects may lead to entirely new notions about the treatment of neurodegenerative
disorders through the manipulation of secondary processes triggered by the adenosine receptor stimulation. On the other hand, it is equally likely that the current exceptions may set the final rule. Thus, the treatment of vascular dementia based on the broad concept of adenosine receptor stimulation is the subject of current clinical tests, and the clinical trials of aspirin and dipyridamole (adenosine uptake inhibitor) have been also concluded very recently. In both cases, the results are highly promising and warrant a larger scale effort. There is no doubt that the present explosive growth of interest in adenosine will have a significant impact on disciplines other than cardiology, where adenosine has been accepted and used for well over a decade.1 It is particularly in the context of the nervous system and its disorders that the attitudes undergo a very rapid change. Until recently, studies of neural effects of adenosine were the domain of the “selected few,” with the majority considering such work as the fringe of the “en vogue” neuroscience. The persistence of those who continued their work was followed by the growing recognition of the paramount importance of adenosine in the modulation of a wide range of phenomena extending well beyond the control of neurotransmitter release. It is, therefore, increasingly likely that the improved understanding of the significance of adenosine in normal and pathological functions of a living organism may ultimately result either in the prophylaxis of stroke or in the therapies aimed at the reduction of poststroke brain damage.
