Related Experiment Video

Updated: Jul 26, 2025

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia
09:35

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

Published on: November 15, 2024

457

Hyperglycemia Aggravates the Cerebral Ischemia Injury via Protein O-GlcNAcylation

Jing Zhu1,2, Xin Ji3,2, Ruirui Shi2

  • 1Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.

Journal of Alzheimer'S Disease : JAD
|June 19, 2023
PubMed

Insights

Protein O-GlcNAcylation worsens ischemic stroke injury in hyperglycemia, contrary to its protective effects in normal conditions. Blocking this modification alleviates injury, suggesting it as a therapeutic target for stroke in diabetic patients.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Alzheimer's disease (AD) patients frequently exhibit cerebrovascular issues, increasing stroke risk.
  • Hyperglycemia exacerbates vascular damage and cerebral ischemia, posing a significant threat.
  • Protein O-GlcNAcylation is known to protect against ischemic stroke, but its role in hyperglycemia-induced exacerbation is unclear.

Purpose of the Study:

  • To investigate the mechanism by which protein O-GlcNAcylation exacerbates cerebral ischemia injury under hyperglycemic conditions.
  • To explore the therapeutic potential of targeting protein O-GlcNAcylation in hyperglycemia-related ischemic stroke.

Main Methods:

  • Utilized high glucose-cultured brain microvascular endothelial (bEnd3) cells subjected to oxygen-glucose deprivation.
  • Assessed cell viability, stroke outcomes, and hemorrhagic transformation in hyperglycemic mice after middle cerebral artery occlusion.
  • Employed Western blot to analyze apoptosis levels and the impact of O-GlcNAcylation modulation.

Main Results:

  • Upregulating O-GlcNAcylation with Thiamet-G attenuated injury in normal glucose but aggravated it in high glucose conditions.
  • In vivo, Thiamet-G worsened ischemic injury and hemorrhagic transformation, increasing apoptosis.
  • Inhibiting O-GlcNAcylation with 6-diazo-5-oxo-L-norleucine ameliorated cerebral injury in hyperglycemic mice.

Conclusions:

  • Protein O-GlcNAcylation plays a critical role in exacerbating cerebral ischemia injury during hyperglycemia.
  • Targeting O-GlcNAcylation presents a potential therapeutic strategy for ischemic stroke in hyperglycemic individuals, including those with AD.
Abstract

Keywords:
Alzheimer’s diseaseO-GlcNAcylationapoptosiscerebral ischemia-reperfusionhemorrhagic transformationhyperglycemia

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