Anales RANF

P.65 PROTECTIVE EFFECT OF THE ADENOSINE A 2B RECEPTOR AGONIST, BAY60-6583, IN A RAT MODEL OF TRANSIENT CEREBRAL ISCHEMIA. L. Gaviano 1 , I. Dettori 1 , I. Bulli 1 , F. Ugolini 1 , D. Lana 1 , M.G. Giovannini 1 and F. Pedata 1 . 1 .University of Florence, Roma, Italy. Cerebral ischemia is today evaluated as the second leading cause of death in major industrialized countries and there is a strong demand for new therapeutic strategies. After ischemic brain injury, extracellular adenosine concentration dramatically increases in the ischemic areas reaching µM concentrations that are able to stimulate all adenosine receptors including the A 2B receptor subtype to which adenosine deserves low affinity. The role of A 2B R in brain ischemia was less studied up to now because of paucity of A 2B R selective agonists and antagonists. The aim of our study was to investigate the effect of the adenosine A 2B receptor agonist, BAY60-6583 (BAY), chronically administered (0.1 mg/kg, i.p., twice/day for 7 days), on ischemic damage parameters in the rat model of focal cerebral ischemia induced by transient (1hour) Middle Cerebral Artery occlusion (tMCAo) by the monofilament technique. Seven days after tMCAo rats were anesthetized and perfused transcardially. Brain infarct volume and and cytoarchitecture of ischemic cortex and striatum were determined by cresyl violet (1%) and hematoxylin/eosin (H&E) staining. BAY, 1, 5 and 7 days after tMCAo, significantly reduced the neurological deficit (score at 7 day: 2.8±0.5, n=6 versus 6.08±0.9, n=4 in vehicle group; p<0.02) evaluated by modified Neurological Severity Score (mNSS) test. Seven days after the ischemic injury, BAY has reduced the volume of the cortical damage (12.60±2.30 mm 3 , n=4 versus 21±1.70 mm 3 , n=3 in vehicle group; p<0.04) and has reduced the number of heterochromatic nuclei both in cortex and striatum (respectively p<0.005; p<0.02). Our preliminary results show that the A 2B R agonist BAY, systemically and chronically administered after ischemia, has reduced the ischemic brain damage and has improved the neurological deficit.