Editors' ChoiceStroke

"Honey, Have You Taken Your Polyphenols Today?"

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Science Translational Medicine  31 Oct 2012:
Vol. 4, Issue 158, pp. 158ec197
DOI: 10.1126/scitranslmed.3005205

Many of us are familiar with the debilitating effects that an ischemic stroke can have on someone close. Although preventive measures are widely adopted and specialized stroke units improve prognosis, recent unsettling reports suggest that stroke risk has shifted to include younger people. With an overall risk of a recurring event after the initial stroke in as many as one out of five cases, emphasis in public health lies on modifying risk and expanding treatment options. Now, Clark and colleagues add to the accumulating evidence that resveratrol, a nutritional polyphenol commonly found in grape skins, berries, and nuts, might have therapeutic value in stroke management.

In a rodent model that emulates the human condition of recurring mild cerebral ischemia, the authors demonstrated that resveratrol protects the brain from further damage. Neuronal cell death, activation of microglia, resident macrophages in brain tissue, and markers of inflammation and oxidative stress were reduced in rats given resveratrol either before the first single stroke or before the recurrent one, both compared with controls. Potential systemic effects of resveratrol—on blood pressure or heart rate, for example—did not explain this finding.

Subsequent mechanistic studies in the same rat model unraveled resveratrol’s role in ameliorating disruptive changes in vascular permeability at the blood-brain barrier that occurs during ischemia; the previously proposed hypothesis that resveratrol improves cerebral blood flow in areas of ischemia was determined to be a less likely mechanism of action. Last, the researchers defined direct cellular effects of resveratrol. Compared with controls, endothelial cells exposed to resveratrol demonstrated better survival in an environment of oxygen and glucose withdrawal. This protection was partially abrogated by blocking the sirtuin SIRT-1, an enzyme associated with various cell functions and activated by resveratrol. The researchers conclude that SIRT-1 activation participates as an underlying mechanism to safeguard the vasculature in the brain from ischemic lesions in recurrent strokes.

The role of sirtuins—not only in stroke and neurodegenerative diseases but also in metabolic disorders such as type 2 diabetes, cardiovascular disease, and cancer—raises the question of whether resveratrol’s beneficial effects can be best harnessed through dietary intake or targeted small-molecule drugs. But first things first: These observations in a mouse model must hold their standing in the context of human disease.

D. Clark et al., Protection against recurrent stroke with resveratrol: Endothelial protection. PLoS One 7, e47792 (2012). [Abstract]

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