title: The Ying and Yang of Adenosine A1and A2AReceptors on ERK1/2 Activation in a Rat Model of Global Cerebral Ischemia Reperfusion Injury.
abstract: Adenosine impacts cerebral ischemia reperfusion (IR) through the inhibitory A1and the excitatory A2receptors. 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
authors.forename: Reham M
authors.initials: RM
authors.lastname: Atef
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
authors.forename: Azza M
authors.initials: AM
authors.lastname: Agha
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Abdel-Rahman A
authors.initials: AA
authors.lastname: Abdel-Rhaman
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt. noha.nassar@pharma.cu.edu.eg.
authors.forename: Noha N
authors.initials: NN
authors.lastname: Nassar
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D019208:Brain-Derived Neurotrophic Factor; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D053148:Caspase 3; D000241:Adenosine
keywords: Adenosine; Global cerebral ischemia reperfusion—pERK1/2; Glutamate—NF-κB; Microglial reactivity