Department of Biochemistry and Molecular Biology, Third Military Medical University, 400038 Chongqing, China.
Rev Neurosci. 2011;22(2):231-9. doi: 10.1515/RNS.2011.020.
This review summarizes recent developments that have contributed to our understanding of how adenosine 2A receptors (A2ARs) modulate brain damage in various animal models of acute neurological injuries, including brain ischemia, traumatic brain injury, spinal cord injury and hemorrhage stroke. The main conclusions are: (1) pharmacological, neurochemical and molecular/genetic approaches to the complex actions of A2AR in different cellular elements suggest that A2AR activation exerts bidirectional effect (detrimental or protective) after brain insults; (2) modulation of glutamate excitotoxicity and neuroinflammation are involved in the protection of A2AR agonists or antagonists, but the bidirectional effect of A2AR is largely due to the bidirectional regulation of neuroinflammation (anti-inflammation or proinflammation) by A2AR on immune cells such as microglia cells and peripheral bone marrow cells; and (3) the bidirectional effect of A2AR on neuroinflammation and brain injury depends on the distinct and sometimes opposite actions of A2AR in various cellular elements and on different injury models and associated pathological conditions. The local glutamate level in the brain injury is one of the crucial factors that contribute to the direction of A2AR effect on neuroinflammation and brain injury outcome. These developments presented here clearly highlight the complexity of using A2AR agents therapeutically in acute neuronal injuries and confirm that A2AR ligands have many promising characteristics that encourage the pursuit of their full therapeutic potential.
这篇综述总结了近期的研究进展，这些进展有助于我们了解腺苷 A2A 受体（A2AR）如何调节各种急性神经损伤动物模型中的脑损伤，包括脑缺血、创伤性脑损伤、脊髓损伤和出血性中风。主要结论如下：（1）通过药理学、神经化学和分子/遗传学方法研究 A2AR 在不同细胞成分中的复杂作用表明，A2AR 激活后对脑损伤具有双向作用（有害或保护）；（2）调节谷氨酸兴奋性毒性和神经炎症参与 A2AR 激动剂或拮抗剂的保护作用，但 A2AR 的双向作用主要归因于 A2AR 对免疫细胞（如小胶质细胞和外周骨髓细胞）的神经炎症的双向调节（抗炎或促炎）；（3）A2AR 对神经炎症和脑损伤的双向作用取决于 A2AR 在不同细胞成分和不同损伤模型及相关病理条件下的独特且有时相反的作用。脑损伤中局部谷氨酸水平是导致 A2AR 对神经炎症和脑损伤结果的作用方向的关键因素之一。这些研究进展清楚地强调了在急性神经元损伤中使用 A2AR 药物的复杂性，并证实 A2AR 配体具有许多有前途的特征，鼓励人们探索其全部治疗潜力。
