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Translational Stroke Research
Published in: Translational Stroke Research 2/2016

01-04-2016 | Original Article

The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Confers Acute Neuroprotection After Intracerebral Hemorrhage in Mice

Authors: Sangeetha Sukumari-Ramesh, Cargill H. Alleyne Jr., Krishnan M. Dhandapani

Published in: Translational Stroke Research | Issue 2/2016

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Abstract

Spontaneous intracerebral hemorrhage (ICH) is a stroke subtype with no effective treatment. Though ICH is known to induce severe neurological damage, the molecular mechanisms of neurological injury after ICH remain largely unclear. Given the emerging role of epigenetic mechanisms in neurodegeneration, the present study evaluated whether suberoylanilide hydroxamic acid (SAHA: vorinostat), a clinically well-tolerated pan-histone deacetylase inhibitor (HDACi), would attenuate neurological injury and improve functional outcomes in a preclinical model of ICH. Mice were administered with SAHA or vehicle after an induction of ICH and acute neuronal death, glial activation, and neurological outcomes were assessed. SAHA-treated mice exhibited less neurodegeneration with concomitant improvement in neurological outcomes than vehicle-treated mice. Furthermore, SAHA downregulated glial activation and the expression of heme oxygenase-1, a stress-inducible enzyme that plays critical roles in neurological damage after ICH. Altogether, the data strongly suggest the role of epigenetic mechanisms in inducing neurological injury after ICH and raise the possible clinical utility of SAHA for therapeutic intervention after ICH.
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Metadata
Title
The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Confers Acute Neuroprotection After Intracerebral Hemorrhage in Mice
Authors
Sangeetha Sukumari-Ramesh
Cargill H. Alleyne Jr.
Krishnan M. Dhandapani
Publication date
01-04-2016
Publisher
Springer US
Published in
Translational Stroke Research / Issue 2/2016
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-015-0421-y

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