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

Translational Stroke Research
Sangeetha Sukumari-RameshKrishnan M Dhandapani

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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Citations

Feb 13, 2016·Journal of Molecular Neuroscience : MN·Sangeetha Sukumari-Ramesh, Cargill H Alleyne
Dec 1, 2015·Journal of Neuroimmunology·Antonietta PicasciaClaudio Napoli
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Aug 30, 2017·Frontiers in Cellular Neuroscience·Frederick BonsackSangeetha Sukumari-Ramesh
Sep 13, 2018·Translational Stroke Research·Xiang LiGang Chen
Jul 25, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Heng YangYuxiang Gu
Jun 4, 2019·Frontiers in Cellular Neuroscience·Frederick Bonsack, Sangeetha Sukumari-Ramesh
Mar 15, 2020·Journal of Molecular Neuroscience : MN·Rajaneekar DasariSangeetha Sukumari-Ramesh
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May 6, 2021·Neuromolecular Medicine·K V AthiraSumana Chakravarty

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