Modulation of ischemic brain injury and neuroinflammation by adenosine A2A receptors

Curr Pharm Des. 2008;14(15):1490-9. Modulation of ischemic brain injury and neuroinflammation by adenosine A2A receptors. Chen JF, Pedata F. SourceDepartment of Neurology, Boston University School of Medicine, 715 Albany Street, E301, Boston, MA 02118, USA. chenjf@bu.edu Abstract Over the past 5 years, the adenosine A(2A) receptor (A(2A)R) is emerging as an attractive therapeutic target for modulating brain injury in a variety of animal models of neurological disorders including stroke. The evidence we have to date indicates that both adenosine and A(2A) antagonists are neuroprotective in ischaemic brain injury. From drug development perspective, administering A(2A) antagonists in association with inhibitors of adenosine kinase may represent a novel strategy for treating stroke. Despite the well-documented neuroprotection by A(2A)R antagonists, the mechanism by which A(2A)Rs affect brain injury remains largely unknown. In this section, we also summarize the experimental evidence for A(2A)R modulation of glial function as possible contribution to the modulation of brain injury. In vitro and in vivo studies reveal that in response to local neuroinflammation following brain insults, time-dependent, inflammatory signal-mediated induction of the A(2A)R in glial cells (particularly microglial cells) make this cell type particularly sensitive to A(2A)R modulation of brain injury. Furthermore, in contrast to the generally held view that the A(2A)R exerts predominantly anti-inflammatory effects (based upon studies in peripheral organs), the A(2A)R modulation of neuroinflammation may differentially affect the outcome of brain injury, depending on the nature of brain insults. Thus, in association with their ability to reduce brain injury, inactivation of the A(2A)R in most models and activation of A(2A)R in some cases have been shown to attenuate brain inflammation through control of the proliferation and production of proinflammatory cytokines. PMID: 18537672