Low doses of the selective adenosine A2A receptor agonist CGS21680 are protective in a rat model of transient cerebral ischemia
Autor: | Felicita Pedata, Lucrezia Cellai, Francesca Corti, Alessia Melani, Maria Giuliana Vannucchi |
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Rok vydání: | 2014 |
Předmět: |
Male
Agonist Adenosine Adenosine A2 Receptor Agonists medicine.drug_class Ischemia Adenosine A2A receptor Blood Pressure Motor Activity Pharmacology Brain Ischemia Brain ischemia Heart Rate Phenethylamines Weight Loss medicine Animals Gliosis Rats Wistar Molecular Biology Cerebral Cortex business.industry General Neuroscience Body Weight medicine.disease Adenosine receptor Corpus Striatum Rats Astrogliosis Disease Models Animal Neuroprotective Agents medicine.anatomical_structure Cerebral cortex Anesthesia Neurology (clinical) business Developmental Biology medicine.drug |
Zdroj: | Brain Research. 1551:59-72 |
ISSN: | 0006-8993 |
Popis: | Evidence indicate that adenosine A2A receptor subtype is of critical importance in stroke. An overexpression of A2A adenosine receptors occurs at central level on neurons and microglia of ischemic striatum and cortex after focal ischemia. Adenosine A2A receptor subtype is localized not only at central level but also peripherally on blood cells, where it is known to exert antiinflammatory effect. Purpose of the present work was to investigate the putative neuroprotective effect of the adenosine A2A receptor agonist CGS21680 in a rat model of transient medial cerebral artery occlusion (MCAo). Transient cerebral ischemia was induced by 1h occlusion of MCA. CGS21680 (0.01 and 0.1mg/kg, i.p.) was administered starting 4h after ischemia according to a chronic protocol (twice/day for 7 days). CGS21680, at the dose of 0.1mg/kg transiently increased heart frequency but did not modify blood pressure. At the dose of 0.01mg/kg the drug did not modify either heart frequency or blood pressure. Following transient MCAo, CGS21680 at both doses protected from neurological deficit from the first day up to 7 days thereafter. At this time, it has reduced microgliosis, astrogliosis and improved myelin organization in the striatum and cytoarchitecture of the ischemic cortex and striatum. Two days after transient MCAo, CGS21680 has reduced the number of infiltrated granulocytes into the ischemic tissue. Data indicate that CGS21680 systemically administered is protective by immunosuppressive effects. |
Databáze: | OpenAIRE |
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