EVIDENCE TO IMPLICATE EARLY MODULATION OF INTERLEUKIN-1 EXPRESSION IN THE NEUROPROTECTION AFFORDED BY 17-ESTRADIOL IN MALE RATS UNDERGONE TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION Olga Chiappetta,* Micaela Gliozzi, z Elisa Siviglia, z Diana Amantea,* Luigi A. Morrone,* ,y Laura Berliocchi,* ,y G. Bagetta,* ,y and M. Tiziana Corasaniti z,} *Department of Pharmacobiology, University of Calabria, Via P. Bucci 87036 Arcavacata di Rende (CS), Italy y UCHAD Center of Neuropharmacology for Normal and Pathological Neuronal Plasticity University of Calabria, Via P. Bucci, 87036 Arcavacata di Rende (CS), Italy z Department of Pharmacobiological Sciences University ‘‘Magna Graecia’’ of Catanzaro, 88100 Catanzaro, Italy } Center for Experimental Neuropharmacology, Mondino-Tor Vergata University of Rome Tor Vergata, 00133 Rome, Italy I. Introduction II. Methods A. Focal Cerebral Ischemia and Drug Treatments B. Neuropathology and Quantification of Ischemic Damage C. Subcellular Fractionation D. Western Blotting E. IL-1 ELISA F. Statistical Analysis III. Results IV. Discussion References Neuroprotection exerted by 17-estradiol (17-E 2 ) has been widely investigated in animal models of acute cerebral ischemia. Estrogens interact with intracellular receptors (ER and ER) to modulate the transcription of target genes, including those implicated in neuronal survival. Neuroprotection may also occur via interac- tion with ER-like membrane receptors mediating rapid, non-genomic, actions or via receptor-independent mechanisms. There is also evidence that blockade of inflam- matory factors may represent an important mechanism involved in estrogenic neuroprotection. Here we investigate whether reduced brain damage by acute pharmacological treatment with 17-E 2 in male rats subjected to transient (2 h) middle cerebral artery occlusion (tMCAo) involves modulation of interleukin-1 (IL-1), a proinflammatory cytokine strongly implicated in the pathophysiology of ischemic stroke. INTERNATIONAL REVIEW OF 357 NEUROBIOLOGY, VOL. 82 Copyright 2007, Elsevier Inc. All rights reserved. DOI: 10.1016/S0074-7742(07)82019-8 0074-7742/07 $35.00