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Updated: Nov 4, 2025
A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia
Published on: November 15, 2024
Effect of hyperglycemia on microglial polarization after cerebral ischemia-reperfusion injury in rats
Ling-di Dong1, Yan-Mei Ma2, Jie Xu2
1Department of Pathology, School of Basic Medical Science, Ningxia Medical University, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Yinchuan, Ningxia 750004, China; Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Abstract:
Hyperglycemia has been shown to aggravate ischemic brain damage, in which the inflammatory reaction induced by hyperglycemia is involved in the worsening of cerebral ischemia-reperfusion injury. However, the role of microglial polarization in hyperglycemia-aggravating cerebral ischemia-reperfusion injury remains unknown. The present study investigated whether diabetic hyperglycemia inhibited or activated microglia, as well as microglial subtypes 1 and 2. Rats were used to establish the diabetic hyperglycemia and middle cerebral artery occlusion (MCAO) model. The markers CD11b, CD16, CD32, CD86, CD206, and Arg1 were used to show M1 or M2 microglia. The results revealed increased neurological deficits, infarct volume, and neural apoptosis in rats with hyperglycemia subjected to MCAO for 30 min and reperfused at 1, 3, and 7 days compared with the normoglycemic rats. Microglia and astrocyte activation and proliferation were inhibited in hyperglycemic rats. Furthermore, M1 microglia polarization was promoted, while that of M2 microglia was inhibited in hyperglycemic rats. These findings suggested that the polarization of M1 and M2 microglia is activated and inhibited, respectively, in hyperglycemic rats and may be involved in the aggravated brain damage caused by ischemia-reperfusion in diabetic hyperglycemia.
Insights
Diabetic hyperglycemia worsens ischemic brain damage by promoting M1 microglia and inhibiting M2 microglia. This microglial polarization shift contributes to increased brain injury after middle cerebral artery occlusion (MCAO) and reperfusion.
Area of Science:
- Neuroscience
- Immunology
- Endocrinology
Background:
- Hyperglycemia exacerbates ischemic brain damage through inflammatory pathways.
- The specific role of microglial polarization in hyperglycemia-induced cerebral ischemia-reperfusion injury is not fully understood.
Purpose of the Study:
- To investigate the effect of diabetic hyperglycemia on microglial activation and polarization (M1/M2 subtypes).
- To determine the involvement of microglial polarization in hyperglycemia-aggravated cerebral ischemia-reperfusion injury.
Main Methods:
- Establishment of a diabetic hyperglycemia and middle cerebral artery occlusion (MCAO) rat model.
- Analysis of neurological deficits, infarct volume, and neural apoptosis at 1, 3, and 7 days post-reperfusion.
- Assessment of microglial and astrocyte activation using markers CD11b, CD16, CD32, CD86, CD206, and Arg1 to identify M1 and M2 subtypes.
Main Results:
- Hyperglycemic rats exhibited increased neurological deficits, infarct volume, and neural apoptosis following MCAO compared to normoglycemic rats.
- Microglia and astrocyte activation and proliferation were suppressed in hyperglycemic rats.
- M1 microglia polarization was promoted, while M2 microglia polarization was inhibited in hyperglycemic rats.
Conclusions:
- Diabetic hyperglycemia promotes M1 microglia polarization and inhibits M2 microglia polarization.
- Altered microglial polarization in hyperglycemia may contribute to aggravated brain damage following cerebral ischemia-reperfusion.
- These findings highlight a potential therapeutic target for mitigating brain injury in diabetic patients experiencing stroke.
