Data from: Early changes in transient adenosine during cerebral ischemia and reperfusion injury

Adenosine is an important neuromodulator in the central nervous system, and tissue adenosine levels increase during ischemic events, attenuating excitotoxic neuronal injury. Recently, our lab developed an electrochemical fast-scan cyclic voltammetry (FSCV) method that identified rapid, spontaneous changes in adenosine concentrations that last only about 3 seconds. Here, we investigated the effects of cerebral ischemia and reperfusion on the concentration and frequency of transient adenosine release in the caudate-putamen. In anesthetized rats, data were collected for four hours: two hours of normoxia, 30 min of cerebral ischemia induced by bilateral common carotid artery occlusion, and 90 min of reperfusion. Transient adenosine release was increased during the cerebral ischemia period and remained elevated during reperfusion. The total number of adenosine transients increased by 52% during cerebral ischemia and reperfusion compared to normoxia. The concentration of adenosine per event did not increase but the cumulative adenosine concentration during cerebral ischemia and reperfusion increased by 53% because of the higher frequency of events. Further, we evaluated the role of A2A antagonist, SCH442416, a putative neuroprotective agent to affect adenosine transients. SCH442416 significantly decreased the transient frequency during cerebral ischemia-reperfusion by 27% and the cumulative concentration by 31%. Our results demonstrate that this mode of rapid adenosine release increases during early cerebral ischemia-reperfusion injury. Rapid adenosine release could provide fast, local neuromodulation and neuroprotection during cerebral ischemia.

腺苷是中枢神经系统中重要的神经调节剂，在缺血事件发生时，组织腺苷水平会升高，从而减轻兴奋性毒性神经元损伤。近期，本课题组开发了一种电化学快速扫描循环伏安法（electrochemical fast-scan cyclic voltammetry, FSCV），可检测到持续时长仅约3秒的腺苷浓度快速自发性变化。本研究旨在探讨脑缺血与再灌注对尾状核-壳核（caudate-putamen）内腺苷瞬时释放的浓度与频率的影响。实验以麻醉大鼠为对象，连续采集4小时的实验数据：包含2小时常氧状态、30分钟由双侧颈总动脉闭塞诱导的脑缺血期，以及90分钟再灌注期。实验结果显示，脑缺血期腺苷瞬时释放事件显著增加，并在再灌注期仍维持在较高水平。与常氧状态相比，脑缺血与再灌注期的腺苷瞬时释放总事件数增加了52%。单次释放事件的腺苷浓度并未出现升高，但由于事件频率提升，脑缺血与再灌注期的腺苷累积释放浓度升高了53%。此外，本研究还评估了A2A受体拮抗剂（A2A antagonist）SCH442416——一种潜在神经保护剂——对腺苷瞬时释放的调控作用。结果表明，SCH442416可使脑缺血再灌注期间的腺苷瞬时释放频率显著降低27%，累积释放浓度降低31%。本研究结果证实，这种快速腺苷释放模式在早期脑缺血再灌注损伤期间显著增强。快速腺苷释放可在脑缺血过程中实现快速的局部神经调节，并发挥神经保护作用。