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Review Open Access

Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review)

  • Authors:
    • Jing Tao
    • Juan Xu
    • Lu Zhou
  • View Affiliations / Copyright

    Affiliations: Department of General Medicine, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing 400014, P.R. China, Department of Gastroenterology Medicine, Chongqing Emergency Medical Center/Chongqing University Central Hospital, Chongqing 400014, P.R. China
    Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 48
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    Published online on: February 18, 2026
       https://doi.org/10.3892/br.2026.2121
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Abstract

Cerebral ischemia‑reperfusion injury (CIRI), a major condition that poses a considerable threat to human health, has high incidence, disability and mortality rates. Mitigating brain damage during reperfusion has been the focal point of research due to the complex physiological and pathological changes that occur during this process. Histone lactylation has garnered considerable attention from researchers as a novel post‑translational modification. Lactate, a metabolic byproduct, regulates gene transcription through histone lactylation, thereby linking cellular metabolism to gene expression programs and contributing to the development of diverse diseases. The present review comprehensively discusses the mechanisms underlying histone lactylation in CIRI and explores its potential clinical applications. The present review aims to offer an understanding of the role of lactylation in CIRI to facilitate the development of novel therapeutic strategies and drugs, and to offer novel insights and directions for the prevention and treatment of CIRI.
View Figures

Figure 1

Schematic of lactate metabolism and
signaling in brain tissue. Glucose enters glycolysis, where an
initial investment of 2 ATP leads to the formation of
fructose-6-phosphate. Through subsequent steps, glycolysis
generates two molecules of pyruvate along with a net yield of 4 ATP
and 2 NADH (plus 2 H+), using 2 NAD+, 2 Pi
and 4 ADP. Pyruvate is then converted to lactate, which is exported
from the cell via MCT4. Extracellular lactate can either be taken
up by neighboring cells through MCT2 to support ATP production and
regulate Arg1 expression, or it can bind to the receptor GPR81 to
trigger signaling pathways. Together, these processes link glucose
metabolism to lactylation-dependent cellular regulation. Arg1,
arginase 1; GPR81, G protein-coupled receptor 81; MCT,
monocarboxylate transporter; P, phosphoryl group; Pi, inorganic
phosphate.

Figure 2

Mechanism of lactylation in
microglial cells during cerebral ischemia-reperfusion injury.
Glucose undergoes glycolysis in damaged cells, producing excess
lactic acid. Lactic acid acts via two paths: Through MCT1/2, it
shifts M1 glia to M2 glia; it also enters cells to upregulate
neurotrophic factors (BDNF and NGF) and anti-inflammatory cytokines
(IL-10 and TGF-β), exerting protective effects. BDNF, brain-derived
neurotrophic factor; MCT, monocarboxylate transporter; NGF, nerve
growth factor.
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Spandidos Publications style
Tao J, Xu J and Zhou L: Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review). Biomed Rep 24: 48, 2026.
APA
Tao, J., Xu, J., & Zhou, L. (2026). Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review). Biomedical Reports, 24, 48. https://doi.org/10.3892/br.2026.2121
MLA
Tao, J., Xu, J., Zhou, L."Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review)". Biomedical Reports 24.4 (2026): 48.
Chicago
Tao, J., Xu, J., Zhou, L."Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review)". Biomedical Reports 24, no. 4 (2026): 48. https://doi.org/10.3892/br.2026.2121
Copy and paste a formatted citation
x
Spandidos Publications style
Tao J, Xu J and Zhou L: Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review). Biomed Rep 24: 48, 2026.
APA
Tao, J., Xu, J., & Zhou, L. (2026). Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review). Biomedical Reports, 24, 48. https://doi.org/10.3892/br.2026.2121
MLA
Tao, J., Xu, J., Zhou, L."Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review)". Biomedical Reports 24.4 (2026): 48.
Chicago
Tao, J., Xu, J., Zhou, L."Histone lactylation modification and its role in cerebral ischemia‑reperfusion injury (Review)". Biomedical Reports 24, no. 4 (2026): 48. https://doi.org/10.3892/br.2026.2121
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