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: Giuseppe Pignataro, Elga Esposito, Rossana Sirabella, Antonio Vinciguerra, Ornella Cuomo, Gianfranco Di Renzo, Lucio Annunziato
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 54 Pg. 105-14 (Jun 2013) ISSN: 1095-953X [Electronic] United States
• PMID: 23454199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Nitric Oxide Synthase Type I
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Blotting, Western
• Brain (blood supply, physiopathology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Femoral Artery
• Gene Knockdown Techniques
• Infarction, Middle Cerebral Artery (metabolism, physiopathology)
• Ischemic Postconditioning
• Male
• Nitric Oxide Synthase Type I (metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley