title: Continuous adenosine A2A receptor antagonism after focal cerebral ischemia in spontaneously hypertensive rats.
abstract: Antagonism of the adenosine A2A receptor (A2AR) has been shown to elicit substantial neuroprotective properties when given immediately after cerebral ischemia. We asked whether the continuous application of a selective A2AR antagonist within a clinically relevant time window will be a feasible and effective approach to treat focal cerebral ischemia. To answer this question, we subjected 20 male spontaneously hypertensive rats to permanent middle cerebral artery occlusion and randomized them equally to a verum and a control group. Two hours after stroke onset, the animals received a subcutaneous implantation of an osmotic minipump filled with 5 mg kg(-1) day(-1) 8-(3-chlorostyryl) caffeine (CSC) or vehicle solution. The serum level of CSC was measured twice a day for three consecutive days. The infarct volume was determined at days 1 and 3 using magnetic resonance imaging. We found the serum level of CSC showing a bell-shaped curve with its maximum at 36 h. The infarct volume was not affected by continuous CSC treatment. These results suggest that delayed and continuous CSC application was not sufficient to treat acute ischemic stroke, potentially due to unfavorable hepatic elimination and metabolization of the pharmaceutical.
authors.affiliation: Translational Centre for Regenerative Medicine, Leipzig, Germany, ulrike.fronz@izi.fraunhofer.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fronz
authors.forename: Alexander
authors.initials: A
authors.lastname: Deten
authors.forename: Frank
authors.initials: F
authors.lastname: Baumann
authors.forename: Alexander
authors.initials: A
authors.lastname: Kranz
authors.forename: Sarah
authors.initials: S
authors.lastname: Weidlich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig
authors.forename: Karen
authors.initials: K
authors.lastname: Nieber
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.forename: Daniel-Christoph
authors.initials: DC
authors.lastname: Wagner
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002110:Caffeine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D058917:Adenosine A2 Receptor Antagonists; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine