Time-course of protection by the selective A2A receptor antagonist SCH58261 after transient focal cerebral ischemia.

Abstract

Evidence indicates that the adenosine A2A receptor subtype is of critical importance in stroke. In previous studies, in the model of permanent middle cerebral artery occlusion (pMCAo), the adenosine A2A receptor antagonist, SCH58261, administered soon after ischemia, proved protective against excessive glutamate outflow in the first 4 h after ischemia and against neurological deficit and tissue damage evaluated 24 h after pMCAo. In the present work, we investigated if neuroprotective effect of SCH58261 was maintained 7 days after transient MCAo (tMCAo). SCH58261 (0.01 mg/kg, i.p.), administered twice/day for 7 days, protected from neurological deficit 1 day after tMCAo, but no more after 5 and 7 days. Two days after tMCAo, SCH58261 did not reduce blood cell infiltration, evaluated as HIS-48 positive cells, into ischemic striatal and cortical tissue. Moreover, 7 days after tMCAo, SCH58261 has not protected ischemic areas from damage and has not ameliorated myelin organization into the ischemic striatum. Protection by the A2A receptor antagonist 24 h after ischemia is attributable to reduced excitotoxicity. Seven days after ischemia the early protective effect of the A2A receptor antagonist likely has been overwhelmed by a secondary damage due to blood cell infiltration and neuroinflammation.

• Authors: Alessia Melani, Ilaria Dettori, Francesca Corti, Lucrezia Cellai, Felicita Pedata
• Journal: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (Neurol Sci) Vol. 36 Issue 8 Pg. 1441-8 (Aug 2015) ISSN: 1590-3478 [Electronic] Italy
• PMID: 25805704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
• Adenosine A2 Receptor Antagonists
• Myelin-Associated Glycoprotein
• Pyrimidines
• Triazoles

Topics

• Adenosine A2 Receptor Antagonists (therapeutic use)
• Analysis of Variance
• Animals
• Blood Cells (drug effects)
• Body Weight (drug effects)
• Brain Injuries (etiology, pathology, prevention & control)
• Disease Models, Animal
• Ischemic Attack, Transient (complications)
• Male
• Myelin-Associated Glycoprotein (metabolism)
• Neurologic Examination
• Pyrimidines (therapeutic use)
• Rats
• Rats, Wistar
• Time Factors
• Triazoles (therapeutic use)