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Abstract
Stroke is a common cause of death worldwide and leads to disability and cognitive dysfunction. Ischemic stroke and hemorrhagic stroke are major categories of stroke, accounting for 68% and 32% of strokes, respectively. Each year, 15 million people experience stroke worldwide, and the stroke incidence is rising. Epigenetic modifications regulate gene transcription and play a major role in stroke. Accordingly, histone deacetylase 1 (HDAC1) participates in DNA damage repair and cell survival. However, the mechanisms underlying the role of HDAC1 in stroke pathogenesis are still controversial. Therefore, we investigated the role of HDAC1 in stroke by using a rat model of endothelin-1-induced brain ischemia. Our results revealed that HDAC1 was deregulated following stroke, and its expressional level and enzymatic activity were decreased. We also used MS-275 to inhibit HDAC1 function in rats exposed to ischemic insult. We found that HDAC1 inhibition promoted the infarct volume, neuronal loss, DNA damage, neuronal apoptosis after stroke, and levels of reactive oxygen species and inflammation cytokines. Additionally, HDAC1 inhibition deteriorated the behavioral outcomes of rats with ischemic insult. Overall, our findings demonstrate that HDAC1 participates in ischemic pathogenesis in the brain and possesses potential for use as a therapeutic target.
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1 Kaohsiung Medical University, Graduate Institute of Medicine, College of Medicine, Kaohsiung, Taiwan (GRID:grid.412019.f) (ISNI:0000 0000 9476 5696); E-Da Dachang Hospital, Department of Neurosurgery, Kaohsiung, Taiwan (GRID:grid.412019.f); E-Da Hospital, Department of Neurosurgery, Kaohsiung, Taiwan (GRID:grid.414686.9) (ISNI:0000 0004 1797 2180); Academia Sinica, Institute of Biomedical Sciences, Taipei, Taiwan (GRID:grid.28665.3f) (ISNI:0000 0001 2287 1366); I-Shou University, School of Medicine, College of Medicine, Kaohsiung, Taiwan (GRID:grid.411447.3) (ISNI:0000 0004 0637 1806)
2 E-Da Hospital, Department of Neurosurgery, Kaohsiung, Taiwan (GRID:grid.414686.9) (ISNI:0000 0004 1797 2180); I-Shou University, School of Medicine for International Students, College of Medicine, Kaohsiung, Taiwan (GRID:grid.411447.3) (ISNI:0000 0004 0637 1806)
3 E-Da Hospital, Department of Neurosurgery, Kaohsiung, Taiwan (GRID:grid.414686.9) (ISNI:0000 0004 1797 2180)
4 Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Department of Obstetrics and Gynecology, Kaohsiung, Taiwan (GRID:grid.145695.a)
5 I-Shou University, School of Medicine for International Students, College of Medicine, Kaohsiung, Taiwan (GRID:grid.411447.3) (ISNI:0000 0004 0637 1806)
6 E-Da Hospital, Department of Neurosurgery, Kaohsiung, Taiwan (GRID:grid.414686.9) (ISNI:0000 0004 1797 2180); I-Shou University, School of Medicine, College of Medicine, Kaohsiung, Taiwan (GRID:grid.411447.3) (ISNI:0000 0004 0637 1806)
7 Academia Sinica, Institute of Biomedical Sciences, Taipei, Taiwan (GRID:grid.28665.3f) (ISNI:0000 0001 2287 1366)
8 I-Shou University, School of Medicine, College of Medicine, Kaohsiung, Taiwan (GRID:grid.411447.3) (ISNI:0000 0004 0637 1806)
9 Kaohsiung Medical University, Graduate Institute of Medicine, College of Medicine, Kaohsiung, Taiwan (GRID:grid.412019.f) (ISNI:0000 0000 9476 5696); Kaohsiung Medical University Hospital, Department of Neurosurgery, Kaohsiung, Taiwan (GRID:grid.412027.2) (ISNI:0000 0004 0620 9374)