Resveratrol and Ischemic Preconditioning in the Brain

Abstract

Cardiovascular pathologies in the French are not prevalent despite high dietary saturated fat consumption. This is commonly referred to as the "French Paradox" attributing its anti-lipidemic effects to moderate consumption of red wine. Resveratrol, a phytoalexin found in red wine, is currently the focus of intense research both in the cardiovascular system and the brain. Current research suggests resveratrol may enhance prognosis of neurological disorders such as, Parkinson's, Huntington's, Alzheimer's diseases and stroke. The beneficial effects of resveratrol include: antioxidation, free radical scavenger, and modulation of neuronal energy homeostasis and glutamatergic receptors/ion channels. Resveratrol directly increases sirtuin 1 (SIRT1) activity, a NAD(+) (oxidized form of nicotinamide adenine dinucleotide)-dependent histone deacetylase related to increased lifespan in various species similar to calorie restriction. We recently demonstrated that brief resveratrol pretreatment conferred neuroprotection against cerebral ischemia via SIRT1 activation. This neuroprotective effect produced by resveratrol was similar to ischemic preconditioning-induced neuroprotection, which protects against lethal ischemic insults in the brain and other organ systems. Inhibition of SIRT1 abolished ischemic preconditioning-induced neuroprotection in CA1 region of the hippocampus. Since resveratrol and ischemic preconditioning-induced neuroprotection require activation of SIRT1, this common signaling pathway may provide targeted therapeutic treatment modalities as it relates to stroke and other brain pathologies. In this review, we will examine common signaling pathways, cellular targets of resveratrol, and ischemic preconditioning-induced neuroprotection as it relates to the brain.

Age-related changes in AMP-activated protein kinase after stroke

“…AMPK enhances SIRT1 activity by increasing cellular NAD+ levels (Canto et al 2009). Although it has been suggested that increased SIRT1 activity leads to extension of life span (Howitz et al 2003;Wood et al 2004), what role SIRT1 plays in the response to ischemic brain insults is unknown (Raval et al 2008;Liu et al 2009a). In the present study, SIRT1 expression was unaffected by age and ischemic injury in vehicle-treated mice.…”

Adaptation and Sensitization to Proteotoxic Stress

“…In support of this notion, ethanol can precondition against models of Alzheimer's disease (Mitchell et al 2009;Collins et al 2010). Other natural dietary compounds, such as the green tea polyphenol epigallocatechin-3-gallate and the red wine ingredient resveratrol have also been proposed as preconditioning agents in Alzheimer's and Parkinson's disease models (Raval et al 2008;Tai and Truong 2010;Tang et al 2011;Wu et al 2012). Resveratrol is thought to protect cells in a sirtuin-dependent manner (Farghali et al 2012;Wu et al 2012).…”

Resveratrol in cardiovascular disease: what is known from current research?

“…Controversial research showed that resveratrol was efficient and promising to prevent cardiac dysfunction after I/R injury, but the beneficial effect of resveratrol was not mediated by NO [101]. Besides the different experiment conditions, SIRT1 and PPARs may be involved in the preconditioning, since SIRT1 and PPARa have been shown to participate in brain protection achieved by resveratrol administration [102,103]. In addition, autophage is a process that cells ''eat/ digest'' autologous macromolecules or organelles, which are damaged under starvation, I/R injury, and other kinds of stress.…”