Evidence map›Paper›PMID 41632031›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Disengaging the Engine: Histone Deacetylases 1 and 2-Mediated Acetylation of Hexokinase-2 Regulates Energy Metabolism in Microglia Following Intracerebral Hemorrhage.

Zhiwen Jiang, Heng Yang, Xinjie Gao, Zengyu Zhang, Ruiyuan Weng, Yuchao Fei, Jiabin Su, Hanqiang Jiang, Wei Ni, Yuxiang Gu

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Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Zhiwen JiangDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.
Heng YangDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.
Xinjie GaoDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.
Zengyu ZhangDepartment of Neurology of Minhang Hospital, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, China.
Ruiyuan WengDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.
Yuchao FeiDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.
Jiabin SuDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.
Hanqiang JiangDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.
Wei NiDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.ORCID 0000-0002-9550-3430
Yuxiang GuDepartment of Neurosurgery, Huashan Hospital of Fudan University, Fudan University, Shanghai, China.ORCID 0000-0002-4580-2205

Funding

Ministry of Science and Technology of the People's Republic of China 2023ZD0505200National Natural Science Foundation of China 82101397National Natural Science Foundation of China 82171313National Natural Science Foundation of China 82271338National Natural Science Foundation of China 82301491National Natural Science Foundation of China 82301492National Natural Science Foundation of China 82471340Natural Science Foundation of Tibet Autonomous Region XZ2020ZR-ZY37(Z)
6 · The paper itself

Abstract

Microglia-mediated neuroinflammation is closely associated with the pathogenesis of secondary brain injury following spontaneous intracerebral hemorrhage (ICH). However, the relationship between immune response regulation and metabolic patterns in microglia remains unclear. Histone Deacetylases 1 and 2, a class of lysine deacetylases, regulates gene transcription by modulating histone acetylation modifications and is widely involved in various cellular activities of microglia. In this study, we observed that knockout of HDAC1/2 in microglia alleviated neurological deficits caused by ICH, preserved white matter integrity, and accelerated hematoma clearance post-ICH. Mechanistically, we found that after ICH, microglia exhibited increased expression of hexokinase 2 (HK2) and enhanced glycolysis. HDAC1/2 knockout/pharmacological inhibition affected the acetylation level of HK2, inhibited its glycolytic activity, and promoted a metabolic shift in activated microglia from glycolysis to fatty acid oxidation. This shift was associated with reduced pro-inflammatory responses and enhanced phagocytic activity in microglia. Enhanced fatty acid oxidation may have a detrimental effect on mitochondrial function, and HDAC1/2 inhibition simultaneously promoted mitophagy in microglia. Additionally, HDAC1/2 inhibition triggered microglial apoptosis and suppressed proliferation, ultimately leading to a reduction in microglial cell numbers. Overall, this study reveals the potential mechanisms by which targeting HDAC1/2, through acetylation modifications and transcriptional regulation, modulates microglial function and metabolism after ICH, thereby exerting protective effects.

Indexed as

Cerebral HemorrhageEnergy MetabolismHexokinaseHistone Deacetylase 1Histone Deacetylase 2MicrogliaAcetylationAnimalsDisease Models, AnimalGlycolysisMaleMiceMice, KnockoutHdac1 protein, mouseHdac2 protein, mouseHexokinasehexokinase 2, mouseHistone Deacetylase 1Histone Deacetylase 2acetylationautophagyfatty acid oxidationglycolysishistone deacetylase 1/2HK2intracerebral hemorrhagemicrogliamitochondrial

Identifiers

PMID41632031
PMCPMC12970280

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.