Hagberg H, Andersson P, Lacarewicz J, Jacobson I, Butcher S, Sandberg M
J Neurochem. 1987 Jul;49(1):227-31. doi: 10.1111/j.1471-4159.1987.tb03419.x.
Extracellular (EC) adenosine, hypoxanthine, xanthine, and inosine concentrations were monitored in vivo in the striatum during steady state, 15 min of complete brain ischemia, and 4 h of reflow and compared with purine and nucleotide levels in the tissue. Ischemia was induced by three-vessel occlusion combined with hypotension (50 mm Hg) in male Sprague-Dawley rats. EC purines were sampled by microdialysis, and tissue adenine nucleotides and purine catabolites were extracted from the in situ frozen brain at the end of the experiment. ATP, ADP, and AMP were analyzed with enzymatic fluorometric techniques, and adenosine, hypoxanthine, xanthine, and inosine with a modified HPLC system. Ischemia depleted tissue ATP, whereas AMP, adenosine, hypoxanthine, and inosine accumulated. In parallel, adenosine, hypoxanthine, and inosine levels increased in the EC compartment. Adenosine reached an EC concentration of 40 microM after 15 min of ischemia. Levels of tissue nucleotides and purines normalized on reflow. However, xanthine levels increased transiently (sevenfold). In the EC compartment, adenosine, inosine, and hypoxanthine contents normalized slowly on reflow, whereas the xanthine content increased. The high EC levels of adenosine during ischemia may turn off spontaneous neuronal firing, counteract excitotoxicity, and inhibit ischemic calcium uptake, thereby exerting neuroprotective effects.
在雄性Sprague-Dawley大鼠中，通过三血管闭塞联合低血压（50 mmHg）诱导缺血，在稳态、15分钟完全脑缺血及4小时再灌注期间，对纹状体内的细胞外（EC）腺苷、次黄嘌呤、黄嘌呤和肌苷浓度进行体内监测，并与组织中的嘌呤和核苷酸水平进行比较。通过微透析采集EC嘌呤，实验结束时从原位冷冻脑中提取组织腺嘌呤核苷酸和嘌呤分解代谢物。采用酶荧光技术分析ATP、ADP和AMP，采用改良的高效液相色谱系统分析腺苷、次黄嘌呤、黄嘌呤和肌苷。缺血使组织ATP耗竭，而AMP、腺苷、次黄嘌呤和肌苷积累。同时，EC区室中的腺苷、次黄嘌呤和肌苷水平升高。缺血15分钟后，腺苷的EC浓度达到40 microM。再灌注时组织核苷酸和嘌呤水平恢复正常。然而，黄嘌呤水平短暂升高（7倍）。在EC区室中，再灌注时腺苷、肌苷和次黄嘌呤含量缓慢恢复正常，而黄嘌呤含量增加。缺血期间EC腺苷的高浓度可能会抑制神经元自发放电、抵消兴奋性毒性并抑制缺血性钙摄取，从而发挥神经保护作用。
