¹Department of Neurology and Neuroscience Program, Cerebral Vascular Disease Research Center, University of Miami School of Medicine, Miami, Florida, USA

Correspondence: Dr MA Pérez-Pinzón, Department of Neurology (D4-5), Cerebral Vascular Disease Research Center, University of Miami School of Medicine, P.O. Box 016960, Miami, Florida 33101, USA. E-mail: perezpinzon@miami.edu

²These authors contributed equally to this work.

Received 16 June 2005; Revised 1 November 2005; Accepted 2 November 2005; Published online 14 December 2005.

Abstract

Recent studies in a variety of species including mammals showed that resveratrol (trans-3, 5, 4"-trihydroxystibene) treatment and caloric restriction increased silent information regulator 2/sirtuin 1 activity, which mediated increase in life span/cell survival. Resveratrol is a naturally occurring phytoalexin and a well-documented cardioprotective agent. Similarly, ischemic preconditioning (IPC) has been shown to be both cardio- and cerebroprotective against subsequent ischemic insults. A major emphasis in this field is to understand the molecular mechanisms that mediate this phenomenon. The goal of this study was to define whether resveratrol can emulate IPC neuroprotection against cerebral ischemia. Employing an in vitro model of cerebral ischemia, the organotypic hippocampal slice culture, we report that resveratrol pretreatment mimics IPC via the SIRT1 pathway. Blockade of SIRT1 activation by sirtinol after IPC or resveratrol pretreatment abolished their neuroprotection. A better understanding of the mechanisms by which resveratrol induces ischemic tolerance in a prophylactic manner may provide a novel therapy against stroke or neurosurgical procedures.