Plasticity of purine release during cerebral ischemia: clinical implications?

Adenosine is a powerful modulator of neuronal function in the mammalian central nervous system. During a variety of insults to the brain, adenosine is released in large quantities and exerts a neuroprotective influence largely via the A1 receptor, which inhibits glutamate release and neuronal activity. Using novel enzyme‐based adenosine sensors, which allow high spatial and temporal resolution recordings of adenosine release in real time, we have investigated the release of adenosine during hypoxia/ischemia in the in vitro hippocampus. Our data reveal that during the early stages of hypoxia adenosine is likely released per se and not as a precursor such as cAMP or an adenine nucleotide. In addition, repeated hypoxia results in reduced production of extracellular adenosine and this may underlie the increased vulnerability of the mammalian brain to repetitive or secondary hypoxia/ischemia.

腺苷是哺乳动物中枢神经系统中神经元功能的一种强大调节剂。在大脑受到多种损伤期间，腺苷会大量释放，并主要通过A1受体发挥神经保护作用，A1受体可抑制谷氨酸释放和神经元活动。利用新型的基于酶的腺苷传感器，它能够对腺苷释放进行高时空分辨率的实时记录，我们研究了体外海马体在缺氧/缺血期间腺苷的释放情况。我们的数据显示，在缺氧早期，腺苷可能是自身释放的，而不是作为诸如环磷腺苷（cAMP）或腺嘌呤核苷酸等前体释放的。此外，反复缺氧会导致细胞外腺苷生成减少，这可能是哺乳动物大脑对反复或继发性缺氧/缺血易感性增加的原因。