TY - JOUR
T1 - The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Confers Acute Neuroprotection After Intracerebral Hemorrhage in Mice
AU - Sukumari-Ramesh, Sangeetha
AU - Alleyne, Cargill H.
AU - Dhandapani, Krishnan M.
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Gliosis
KW - Microglial activation
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=84959493769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959493769&partnerID=8YFLogxK
U2 - 10.1007/s12975-015-0421-y
DO - 10.1007/s12975-015-0421-y
M3 - Article
C2 - 26338677
AN - SCOPUS:84959493769
SN - 1868-4483
VL - 7
SP - 141
EP - 148
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 2
ER -