HDAC inhibition reduces white matter injury after intracerebral hemorrhage

Heng Yang; Wei Ni; Pengju Wei; Sicheng Li; Xinjie Gao; Jiabin Su; Hanqiang Jiang; Yu Lei; Liangfu Zhou; Yuxiang Gu

doi:10.1177/0271678x20942613

journal article Jul 23, 2020

HDAC inhibition reduces white matter injury after intracerebral hemorrhage

Heng Yang

Wei Ni

Pengju Wei Sicheng Li

Xinjie Gao Jiabin Su Hanqiang Jiang Yu Lei

Liangfu Zhou Yuxiang Gu

Journal of Cerebral Blood Flow & Metabolism Vol. 41 No. 5 pp. 958-974 · SAGE Publications

View at Publisher Save 10.1177/0271678x20942613

Abstract

Inhibition of histone deacetylases (HDACs) has been shown to reduce inflammation and white matter damage after various forms of brain injury via modulation of microglia/macrophage polarization. Previously we showed that the HDAC inhibitor scriptaid could attenuate white matter injury (WMI) after ICH. To access whether modulation of microglia/macrophage polarization might underlie this protection, we investigated the modulatory role of HDAC2 in microglia/macrophage polarization in response to WMI induced by intracerebral hemorrhage (ICH) and in primary microglia and oligodendrocyte co-cultures. HDAC2 activity was inhibited via conditional knockout of the Hdac2 gene in microglia or via administration of scriptaid. Conditional knockout of the Hdac2 gene in microglia and HDAC inhibition with scriptaid both improved neurological functional recovery and reduced WMI after ICH. Additionally, HDAC inhibition shifted microglia/macrophage polarization toward the M2 phenotype and reduced proinflammatory cytokine secretion after ICH in vivo. In vitro, a transwell co-culture model of microglia and oligodendrocytes also demonstrated that the HDAC inhibitor protected oligodendrocytes by modulating microglia polarization and mitigating neuroinflammation. Moreover, we found that scriptaid decreased the expression of pJAK2 and pSTAT1 in cultured microglia when stimulated with hemoglobin. Thus, HDAC inhibition ameliorated ICH-mediated neuroinflammation and WMI by modulating microglia/macrophage polarization.

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References

Details

Published: Jul 23, 2020
Vol/Issue: 41(5)
Pages: 958-974
License: View

Authors

H

Heng Yang

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

W

Wei Ni

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

P

Pengju Wei

State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai, China

S

Sicheng Li

State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai, China

X

Xinjie Gao

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

J

Jiabin Su

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

H

Hanqiang Jiang

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

Y

Yu Lei

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

L

Liangfu Zhou

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

Y

Yuxiang Gu

Department of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China

Cite This Article

Heng Yang, Wei Ni, Pengju Wei, et al. (2020). HDAC inhibition reduces white matter injury after intracerebral hemorrhage. Journal of Cerebral Blood Flow & Metabolism, 41(5), 958-974. https://doi.org/10.1177/0271678x20942613

HDAC inhibition reduces white matter injury after intracerebral hemorrhage

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