Blockade of A(2A) adenosine receptors leads to c-fos inhibition in a rat model of brain ischemia.
Adenosine plays an important role in cerebral ischemia by acting on its own receptors, in particular the A(2A)receptor. Its activation leads to excitatory amino acid release thus contributing to the ischemic damage. Blockade by specific antagonists may protect against cytotoxic injury. Our study was aimed to investigate the effect of the blockade of A(2A)receptors, by Sch 58261, on the expression of the early gene c-fos, in a model of permanent middle cerebral artery occlusion (pMCAo), in rats. In the pMCAo model, ischemia was induced in the right hemisphere whereas the contralateral one was considered the control. In our study, we have compared pMCAo rats, pMCAo rats treated with Sch 58261 and sham operated ones.C-fos was markedly expressed in the ischemic hemispheres, whereas lower levels were detected in the contralateral ones of the ischemic animals. The lowest bands were observed in sham operated rats. After treatment with Sch 58261, a considerable reduction in c-fos expression was observed in the ischemic hemispheres, whereas a limited effect was detected in the others. Our results suggest that inhibition of immediate-early gene expression by the A(2A)receptors antagonist Sch 58261 may contribute to its neuroprotective activity.
Petroni
A
A
Department of Pharmacological Sciences, University of Milan, via Balzaretti 9, Milan, 20133, Italy. anna.petroni@unimi.it
Papini
N
N
Blasevich
M
M
Galli
C
C
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D014230:Triazoles / Q000494:pharmacology*
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D016760:Proto-Oncogene Proteins c-fos; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles