Resveratrol Preconditioning Induces a Novel Extended Window of Ischemic Tolerance in the Mouse Brain

This could be great. Just ask your doctor to calculate the amount of red wine needed to be consumed to ramp up from the rat/mouse body size to your human size. And since this is preconditioning and we have no idea on when our next stroke will come, it logically means we should be consuming red wine every 14 days.

This could be tongue in cheek but your doctor needs to be able to answer the question anyways since there is no other damage prevention protocol out there. You have to create your own prevention steps since your doctor has no concrete actions to prevent stroke damage from your next stroke.

Resveratrol Preconditioning Induces a Novel Extended Window of Ischemic Tolerance in the Mouse Brain

1. Kevin B. Koronowski, BS,
2. Kunjan R. Dave, PhD,
3. Isabel Saul, BS,
4. Vladimir Camarena, PhD,
5. John W. Thompson, PhD,
6. Jake T. Neumann, PhD,
7. Juan I. Young, PhD and
8. Miguel A. Perez-Pinzon, PhD

+ Author Affiliations

1. From the Cerebral Vascular Disease Research Laboratories (K.B.K., K.R.D., I.S., J.W.T., J.T.N., M.A.P.-P.), Department of Neurology (K.B.K., K.R.D., I.S., J.W.T., J.T.N., M.A.P.-P.), and Neuroscience Program (K.B.K., K.R.D., J.I.Y., M.A.P.-P.), Hussman Institute for Human Genetics (V.C., J.I.Y.), University of Miami Miller School of Medicine, Miami, FL.

1. Correspondence to Miguel A. Perez-Pinzon, PhD, Department of Neurology, D4-5, University of Miami, Miller School of Medicine, PO Box 016960, Miami, FL 33101. E-mail perezpinzon@miami.edu

Abstract

Background and Purpose—Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered 2 days before global ischemia in rats. This protection is linked to silent information regulator 2 homologue 1 (Sirt1) and enhanced mitochondrial function possibly through its repression of uncoupling protein 2. Brain-derived neurotrophic factor (BDNF) is another neuroprotective protein associated with Sirt1. In this study, we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice.

Methods—We tested 4 different RPC paradigms against a middle cerebral artery occlusion model of stroke. Infarct volume and neurological score were calculated 24 hours after middle cerebral artery occlusion. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions, and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay.

Results—Although repetitive RPC induced neuroprotection from middle cerebral artery occlusion, strikingly one application of RPC 14 days before middle cerebral artery occlusion showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days after RPC, Sirt1 protein was increased 1.5-fold and differentially bound to the uncoupling protein 2 and BDNF promoter regions. Accordingly, synaptic uncoupling protein 2 level decreased by 23% and cortical BDNF concentration increased 26%.

Conclusions—RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1 through upregulation of BDNF and downregulation of uncoupling protein 2.