ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Non-Neuronal Cells
Microglial histone deacetylase-3 conditional deletion attenuates neurological deficits after intracerebral hemorrhage
Provisionally accepted
- Augusta University, Augusta, United States
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Stimulation of the innate immune system after intracerebral hemorrhage (ICH), characterized by microglial activation, contributes to ICH-induced neuroinflammation and brain damage. Despite the efficacy of broad-spectrum histone deacetylase (HDAC) inhibitors in improving acute neurological outcomes after ICH, the isoform-or cell-specific roles of histone deacetylases (HDACs) after ICH remain largely understudied. Given the emerging role of HDAC3 in various neuropathological conditions, we herein evaluate the functional role of microglial HDAC3 after ICH using newly developed microglia-specific HDAC3 conditional knockout mice (cKO). The microglia-specific conditional deletion of HDAC3 in male and female mice improved acute and long-term neurobehavioral outcomes following ICH. Furthermore, conditional deletion of HDAC3 in microglia significantly attenuated the expression of proinflammatory mediators, such as Nos2, S100A9, TNF-α, and IL-6, and augmented the expression of anti-inflammatory mediators, such as Arg-1, in the ipsilateral brain region following ICH. This observation was found to be concomitant with a reduction in the number of Iba1-positive cells, further implicating attenuation of neuroinflammatory response after ICH. Moreover, conditional deletion of HDAC3 in microglia did not alter hematoma volume after ICH, suggesting that the observed effects are independent of hematoma size. Overall, the data implicate a novel role of microglial HDAC3 in regulating neurological deficits after ICH in male and female subjects.
Keywords: Epigenetic mechanisms, HDAC3, Histone Deacetylases, Inflammation, intracerebral hemorrhage
Received: 28 Oct 2025; Accepted: 22 Jan 2026.
Copyright: © 2026 Watson, Xu and Sukumari Ramesh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sangeetha Sukumari Ramesh
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