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Continuous adenosine A2A receptor antagonism after focal cerebral ischemia in spontaneously hypertensive rats
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Fronz, Ulrike, Deten, Alexander, Baumann, Frank, Kranz, Alexander, Weidlich, Sarah, Härtig, Wolfgang, Nieber, Karen, Boltze, Johannes and Wagner, Daniel-Christoph (2014) Continuous adenosine A2A receptor antagonism after focal cerebral ischemia in spontaneously hypertensive rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 387 (2). pp. 165-173. doi:10.1007/s00210-013-0931-7
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Official URL: http://dx.doi.org/10.1007/s00210-013-0931-7
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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Naunyn-Schmiedeberg's Archives of Pharmacology | ||||
| Publisher: | Springer | ||||
| ISSN: | 0028-1298 | ||||
| Official Date: | February 2014 | ||||
| Dates: |
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| Volume: | 387 | ||||
| Number: | 2 | ||||
| Page Range: | pp. 165-173 | ||||
| DOI: | 10.1007/s00210-013-0931-7 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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