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Int J Physiol Pathophysiol Pharmacol 2011;3(1):1-8

Original Article
ASIC1a contributes to neuroprotection elicited by ischemic preconditioning and

Giuseppe Pignataro, Ornella Cuomo, Elga Esposito, Rossana Sirabell, Gianfranco Di Renzo, Lucio Annunziato

Division of Pharmacology, Department of Neuroscience, School of Medicine, “Federico II” University of Naples, Via Pansini, 5, 80131,
Naples, Italy; Fondazione IRCCS SDN, Via Gianturco, 113, 80143, Naples, Italy.

Received August 7, 2010; Accepted September 8, 2010; Epub September 10, 2010; Published January 1, 2011.

Abstract: Acid-sensing ion channels, ASICs, are proton-gated cation channels widely expressed in peripheral sensory neurons and in
neurons of the central nervous system that play an important role in a variety of physiological and pathological processes. To further
confirm the neuroprotective role played by ASIC1a in cerebral ischemia, its role has been here examined in two endogenous recently
characterized neuroprotective strategies: brain ischemic preconditioning and postconditioning. The well known family of Mitogen
Activated Kinases (MAPK) has been proposed as important mediator of these neuroprotective mechanisms. The main aim of this study
was to elucidate whether ASIC1a might take part as effector in the neuroprotection evoked by brain ischemic preconditioning and
postconditioning. For this purpose we investigated the effect of ischemic preconditioning and postconditioning on (1) ASIC1a mRNA
and protein expression in the temporoparietal cortex of rats at different time intervals; and (2) the effect of p-AKT inhibition on ASIC1a
expression during ischemic preconditioning and postconditioning. Ischemic preconditioning and postconditioning were experimentally
induced in adult male rats by subjecting them to different protocols of middle cerebral artery occlusion and reperfusion. ASIC1a
expression was dramatically reduced in both the neuroprotective processes. These changes in ASIC expression were p-AKT mediated,
since LY-294002, a specific p-AKT inhibitor, was able to  prevent variations in ASIC1a expression. The results of the present study
support the idea that the downregulation of ASIC1a expression and activity might be a reasonable strategy to reduce the infarct
extension after stroke. (IJPPP1008003).

Keywords: ASIC1a, preconditioning, postconditioning, stroke, neuroprotection

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Address all correspondence to:
Lucio Annunziato, MD
Division of Pharmacology, Department of Neuroscience
School of Medicine, “Federico II” University of Naples
Via Pansini 5, 80131 Naples, Italy.
Tel: +39-81-7463318
Fax: +39-81-7463323
E-mail: lannunzi@unina.it