Journal
STROKE
Volume 40, Issue 8, Pages 2899-2905Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.108.540229
Keywords
focal ischemia; histone deacetylase inhibitors; neuroprotection; plasticity; memory
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Funding
- Adelson Medical Research Foundation
- New York State Department of Health
- Burke Foundation
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Achieving therapeutic efficacy in ischemic stroke represents one of the biggest challenges in translational neurobiology. Despite extensive efforts, tissue plasminogen activator remains the only available intervention for enhancing functional recovery in humans once a stroke has occurred. To expand the repertoire of therapeutic options in stroke, one must consider and target its diverse pathophysiologies that trigger cell loss in a manner that also permits and enhances neuronal plasticity and repair. Several converging lines of inquiry suggest that histone deacetylase (HDAC) inhibition could be a strategy to achieve these goals. Here, we review evidence that targeting HDACs with low-molecular-weight inhibitors significantly decreases neuronal injury and improves functional outcome in multiple preclinical models of focal ischemia. These salutary effects emanate, in part, from modifications of chromatin and nonchromatin proteins that enhance adaptive gene expression or adaptive protein function. Together, the findings suggest that HDAC inhibition is a strategy capable of targeting diverse pathophysiologies of stroke with a wide therapeutic window. (Stroke. 2009; 40: 2899-2905.)
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