Chronic administration of adenosine A(3) receptor agonist and cerebral ischemia: neuronal and glial effects

We have previously shown that chronic administration of the selective A, re ceptor agonist N-6-(3-iodobenzyl)-5'-N-methylcarboxoamidoadenosine (IB-MECA ) leads to a significant improvement of postocclusive cerebral blood flow, and protects against neuronal damage and mortality induced by severe forebr ain ischemia in gerbils. Using immunocytochemical methods we now show that chronic with IB-MECA results in a significant preservation of ischemia-sens itive microtubule associated protein 2 (MAP-2), enhancement of the expressi on of glial fibrillary acidic protein (GFAP), and a very intense depression of nitric oxide synthase in the brain of postischemic gerbils. These chang es demonstrate that the cerebroprotective actions of chronically administer ed IB-MECA involve both neurons and glial cells, and indicate the possibili ty of distinct mechanisms that are affected in the course of chronic admini stration of the drug. (C) 1999 Elsevier Science B.V. All rights reserved.