title: Modulation of cerebral RAGE expression following nitric oxide synthase inhibition in rats subjected to focal cerebral ischemia.
abstract: The receptor for advanced glycation endproducts (RAGE) is a key mediator of neuroinflammation following cerebral ischemia. Nitric oxide (NO) plays a dualistic role in cerebral ischemia, depending on whether it originates from neuronal, inducible or endothelial synthase. Although a dynamic interplay between RAGE and NO pathways exists, its relevance in ischemic stroke has not been investigated. The aim of this study is to evaluate the effect of the NO synthase (NOS) inhibition on RAGE expression in rats subjected to transient middle cerebral artery occlusion (tMCAo). Full-length (fl-RAGE) gene expression was elevated in the striatum and, to a lesser extent, in the cortex of rats undergone tMCAo. The exacerbation of cortical damage caused by systemic administration of L-N-(1-iminoethyl)ornithine (L-NIO), a relatively selective inhibitor of endothelial NOS (eNOS), was associated with elevated mRNA levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and fl-RAGE in both the cortex and the striatum. Conversely, NG-nitro-l-arginine methyl ester (L-NAME), a non-selective NOS inhibitor, decreased cortical damage, did not affect cerebral cytokine mRNA levels, while it increased fl-RAGE mRNA expression only in the striatum. Fl-RAGE striatal protein levels varied accordingly with observed mRNA changes in the striatum, while in the cortex, RAGE protein levels were reduced by tMCAo and further decreased following L-NIO treatment. Modulation of RAGE expression by different inhibitors of NOS may have opposite effects on transient cortical ischemia: the non selective inhibition of NOS activity is protective, while the selective inhibition of eNOS is harmful, probably via the activation of inflammatory pathways.
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Pavia, Italy. Electronic address: rosaria.greco@mondino.it.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Greco
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Pavia, Italy; Department of Brain and Behavioural Sciences, University of Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Demartini
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Pavia, Italy; Department of Brain and Behavioural Sciences, University of Pavia, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Zanaboni
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino" National Neurological Institute, Pavia, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Amantea
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Pavia, Italy; Department of Brain and Behavioural Sciences, University of Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tassorelli
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: Cerebral ischemia/reperfusion; Cytokines; Full-length RAGE; L-NAME; L-NIO