Blocking adenosine A2A receptors during oxigen-glucose deprivation delays anoxic depolarization and ameliorates neuronal survival in the rat CA1 hippocampus

The role of adenosine A2A receptor activation during oxygen and glucose deprivation (OGD) was investigated using extracellular recordings of field excitatory post-synaptic potentials (fEPSPs) from the CA1 region of hippocampal slices, acutely prepared from 2-month-old rats. The cell-death marker propidium iodide (PI) uptake was used to evaluate cell viability before and after OGD application.Seven and 30-min OGD elicit an irreversible loss of fEPSP and were invariably followed by the appearance of anoxic depolarization (AD), an unambiguous sign of neuronal damage. The application of the selective adenosine A2A receptor antagonist 4–2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-yl-amino]ethyl phenol (ZM 241385, 100– 500 nM., n=32) did not modify the fEPSP outcome during OGD, but significantly prevented or delayed AD appearance during 30 min OGD: from 6.8±0.3 min, n=11 in the absence to 9.0±0.4 min, n=11 in the presence of A2A antagonist) and permits a significant (P<0.001) recovery of neurotransmission after 7-min OGD (94.4±5.0%, n=22, in comparison to 5.4± 2.8%, n=24 found in untreated OGD slices). In related experiments, slices were subjected to 7 min OGD followed, after 2 hours from the end of OGD, by 1 hour staining with the PI (5 μg/ml). Substantial CA1 pyramidal neuronal damage occurred in OGD untreated slices that was significantly decreased by 100 nM. ZM 241385. Data indicate that the selective block of adenosine A2A receptors provides neuroprotection after severe OGD in the CA1 region of rat hippocampus.