This Article Full Text Full Text (PDF) All Versions of this Article: 40/8/2899    most recent STROKEAHA.108.540229v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Langley, B. Articles by Rivieccio, M. A. PubMed PubMed Citation Articles by Langley, B. Articles by Rivieccio, M. A. Related Collections Behavioral/psychosocial - stroke Acute Cerebral Infarction Behavioral Changes and Stroke Neuroprotectors Other Stroke Treatment - Medical

(Stroke. 2009;40:2899.)
© 2009 American Heart Association, Inc.

Topical Review

Targeting Histone Deacetylases as a Multifaceted Approach to Treat the Diverse Outcomes of Stroke

Brett Langley, PhD; Camille Brochier, PhD Mark A. Rivieccio, PhD

From the Burke Medical Research Institute, White Plains, NY; and the Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York.

Correspondence to Brett Langley, PhD, Burke/Cornell Medical Research Institute, 785 Mamaroneck Road, White Plains, NY 10605. E-mail bcl2002{at}med.cornell.edu

David Alexander MD Lalit Kalra MD Section Editors:

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.

Key Words: focal ischemia • histone deacetylase inhibitors • neuroprotection • plasticity • memory

This article has been cited by other articles:

				M. A. Rivieccio, C. Brochier, D. E. Willis, B. A. Walker, M. A. D'Annibale, K. McLaughlin, A. Siddiq, A. P. Kozikowski, S. R. Jaffrey, J. L. Twiss, et al. HDAC6 is a target for protection and regeneration following injury in the nervous system PNAS, November 17, 2009; 106(46): 19599 - 19604. [Abstract] [Full Text] [PDF]