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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 387, Issue 2, pp 165–173 | Cite as

Continuous adenosine A2A receptor antagonism after focal cerebral ischemia in spontaneously hypertensive rats

  • Ulrike FronzEmail author
  • Alexander Deten
  • Frank Baumann
  • Alexander Kranz
  • Sarah Weidlich
  • Wolfgang Härtig
  • Karen Nieber
  • Johannes Boltze
  • Daniel-Christoph Wagner
Original Article

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.

Keywords

Brain ischemia Stroke SHR rat Adenosine A2A receptor 8-CSC 

Notes

Acknowledgment

The authors thank Dr. Jens Grosche, Prof. Rainer Preiß, Jutta Ortwein, and Ute Bauer for constructive discussion and excellent technical assistance.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ulrike Fronz
    • 1
    • 2
    • 3
    Email author
  • Alexander Deten
    • 1
    • 3
  • Frank Baumann
    • 4
  • Alexander Kranz
    • 1
    • 3
  • Sarah Weidlich
    • 2
    • 3
  • Wolfgang Härtig
    • 5
  • Karen Nieber
    • 2
  • Johannes Boltze
    • 1
    • 3
  • Daniel-Christoph Wagner
    • 1
    • 3
  1. 1.Translational Centre for Regenerative MedicineLeipzigGermany
  2. 2.Institute of PharmacyUniversity of LeipzigLeipzigGermany
  3. 3.Fraunhofer Institute for Cell Therapy and ImmunologyLeipzigGermany
  4. 4.Institute of Laboratory Medicine, Clinical Chemistry and Molecular DiagnosticsUniversity of LeipzigLeipzigGermany
  5. 5.Paul Flechsig Institute for Brain ResearchUniversity of LeipzigLeipzigGermany

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