title: nNOS and p-ERK involvement in the neuroprotection exerted by remote postconditioning in rats subjected to transient middle cerebral artery occlusion.
abstract: It has recently been hypothesized that a sub-lethal ischemic insult induced in one organ is able to protect from a harmful ischemia occurring in a different organ. The objective of this study is to identify new putative mechanisms of neuroprotection elicited by remote ischemic femoral postconditioning. A 50% reduction in the infarct volume was observed when 100min of middle cerebral artery occlusion was followed, 10min later, by the remote postconditioning stimulus represented by 20min of femoral artery occlusion. The use of in vivo silencing strategy allowed to demonstrate that NO production through nNOS mediates part of the neuroprotection. Indeed, whereas CNS nNOS expression was up-regulated by remote postconditioning, the pharmacological inhibition of nNOS or its silencing-mediated knocking-down partially prevented this neuroprotective effect. This nNOS overexpression seemed to be p-ERK dependent. In fact, p-ERK expression increased in brain cortex after remote postconditioning, and its pharmacological inhibition prevented both nNOS overexpression and remote postconditioning-mediated neuroprotection. Interestingly, neuroprotection induced by remote postconditioning was partially prevented when ganglion transmission was pharmacologically interrupted by hexamethonium, thus showing that neural factors are involved in this phenomenon. Collectively, the present study demonstrates that p-ERK and nNOS take part to the complex cascade of events triggered by ischemic remote postconditioning.
authors: Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy.
authors: Giuseppe
authors: G
authors: Pignataro
authors: Elga
authors: E
authors: Esposito
authors: Rossana
authors: R
authors: Sirabella
authors: Antonio
authors: A
authors: Vinciguerra
authors: Ornella
authors: O
authors: Cuomo
authors: Gianfranco
authors: G
authors: Di Renzo
authors: Lucio
authors: L
authors: Annunziato
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005263:Femoral Artery; D055785:Gene Knockdown Techniques; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000503:physiopathology; D057775:Ischemic Postconditioning; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D052248:Nitric Oxide Synthase Type I; D048049:Extracellular Signal-Regulated MAP Kinases