title: SCH58261 the selective adenosine A(2A) receptor blocker modulates ischemia reperfusion injury following bilateral carotid occlusion: role of inflammatory mediators.
abstract: In the present study, the effects of SCH58261, a selective adenosine A(2A) receptor antagonist that crosses the blood brain barrier (BBB) and 8-(4-sulfophenyl) theophylline (8-SPT), a non-selective adenosine receptor antagonist that acts peripherally, were investigated on cerebral ischemia reperfusion injury (IR). Male Wistar rats (200-250 g) were divided into four groups: (1) sham-operated (SO), IR pretreated with either (2) vehicle (DMSO); (3) SCH58261 (0.01 mg/kg); (4) 8-SPT (2.5 mg/kg). Animals were anesthetized and submitted to occlusion of both carotid arteries for 45 min. All treatments were administered intraperitoneally (i.p.) post carotid occlusion prior to exposure to a 24 h reperfusion period. Ischemic rats showed increased infarct size compared to their control counterparts that corroborated with histopathological changes as well as increased lactate dehydrogenase (LDH) activity in the hippocampus. Moreover, ischemic animals showed habituation deficit, increased anxiety and locomotor activity. IR increased hippocampal glutamate (Glu), GABA, glycine (Gly) and aspartate (ASP). SCH58261 significantly reversed these effects while 8-SPT elicited minimal change. IR raised myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), prostaglandin E₂ (PGE₂) accompanied by a decrease in interleukin-10 (IL-10), effects that were again reversed by SCH58261, but 8-SPT elicited less changes. Results from the present study point towards the importance of central blockade of adenosine A(2A) receptor in ameliorating hippocampal damage following IR injury by halting inflammatory cascades as well as modulating excitotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
authors.forename: R A
authors.initials: RA
authors.lastname: Mohamed
authors.forename: A M
authors.initials: AM
authors.lastname: Agha
authors.forename: N N
authors.initials: NN
authors.lastname: Nassar
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology*; D018836:Inflammation Mediators / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000596:Amino Acids; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D011743:Pyrimidines; D014230:Triazoles; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase
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