The biphasic regulatory effect of adenosine A2B receptor in ischemic brain injury and its therapeutic potential

Ischemic brain injury is the leading cause of neurological disability and death worldwide. Adenosine A2B receptor (A2BR) is a member of the G protein-coupled receptor family, playing a crucial role in regulating excitotoxicity, inflammation, cell apoptosis, and vascular homeostasis. New evidence suggests that adenosine A2BR has a biphasic, time-dependent effect on ischemic brain injury. Its antagonists exhibit neuroprotective effects in the acute phase, while agonists have anti-inflammatory and vascular protective effects in the later stage, providing a new therapeutic direction for improving the long-term prognosis of patients with ischemic brain injury. This article reviews the research progress of A2BR in ischemic brain injury, including its molecular structure, expression kinetics, cell distribution, mechanism of action, pharmacological intervention, and systemic significance. We also discussed the therapeutic prospects of targeting A2BR and provided future prospects for personalized treatment strategies.