The Ying and Yang of Adenosine A1 and A2A Receptors on ERK1/2 Activation in a Rat Model of Global Cerebral Ischemia Reperfusion Injury.
Adenosine impacts cerebral ischemia reperfusion (IR) through the inhibitory A1 and the excitatory A2 receptors. The present study aimed at investigating the contrasting role of pERK1/2 in mediating adenosine A1R (protective) versus A2AR (deleterious) effects in IR. Male Wistar rats subjected to bilateral carotid occlusion (45 min) followed by reperfusion (24 h) exhibited increased pERK1/2 activity, downstream from DAG pathway, along with increases in hippocampal glutamate, c-Fos, NF-κB, TNF-α, iNOS, TBARS, cytochrome c, caspase-3, BDNF, Nrf2, and IL-10 contents. Further, hippocampal microglial reactivity, glial TNF-α, and BDNF expression were observed. Although unilateral intrahippocampal injection of either the A1R agonist CHA or the A2AR agonist CGS21680 increased pERK1/2, only CHA mitigated histopathological and behavioral deficits along with reducing glutamate, microglial activation, c-Fos, TNF-α, iNOS, TBARS, cytochrome c and caspase-3 and elevating Nrf2 and IL-10 levels in IR rats. These results yield insight into the double-faceted nature of pERK1/2 in mediating protective and deleterious effects of A1R and A2AR signaling, respectively, against IR injury.
['Atef|Reham M|RM|', 'Agha|Azza M|AM|', 'Abdel-Rhaman|Abdel-Rahman A|AA|', 'Nassar|Noha N|NN|']
D000241:Adenosine D058907:Adenosine A1 Receptor Agonists D058908:Adenosine A2 Receptor Agonists D000818:Animals D001522:Behavior, Animal D019208:Brain-Derived Neurotrophic Factor D053148:Caspase 3 D004195:Disease Models, Animal D006624:Hippocampus D020935:MAP Kinase Signaling System D008297:Male D018782:Maze Learning D008568:Memory D017628:Microglia D009048:Motor Skills D010627:Phenethylamines D010766:Phosphorylation D051381:Rats D017208:Rats, Wistar D043682:Receptor, Adenosine A1 D043705:Receptor, Adenosine A2A D015427:Reperfusion Injury D017392:Thiobarbituric Acid Reactive Substances D014409:Tumor Necrosis Factor-alpha
Adenosine Microglial reactivity Global cerebral ischemia reperfusion—pERK1/2 Glutamate—NF-κB