Age-related reduction of cerebral ischemic preconditioning: myth or reality?

David Della-Morte,1,2 Francesco Cacciatore,3 Elisa Salsano,4 Gilda Pirozzi,4 Maria Teresa Del Genio,4 Iole D'Antonio,4 Gaetano Gargiulo,5 Raffaele Palmirotta,2 Fiorella Guadagni,2 Tatjana Rundek,1 Pasquale Abete41Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA; 2Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele, Rome, Italy; 3Istituto Scientifico di Campoli/Telese, Fondazione Salvatore Maugeri, IRCCS, Benevento, Italy; 4Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II," Naples, Italy; 5AON, SS Antonio e Biagio e Cesare Arrigo, Struttura Complessa di Geriatria, Alessandria, ItalyAbstract: Stroke is one of the leading causes of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. The “cerebral” ischemic preconditioning mechanism is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators released and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Agents able to mimic the “cerebral” preconditioning effect may represent a new powerful tool for the treatment of acute ischemic stroke in the elderly. In this article, animal and human cerebral ischemic preconditioning, its age-related difference, and its potential therapeutical applications are discussed.Keywords: ischemic preconditioning, stroke, transient cerebral ischemic attack, mortality, elderly