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Updated: Jul 5, 2025
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Microglia/macrophage polarization regulates spontaneous remyelination in intermittent cuprizone model of
Davood Zarini1, Parichehr Pasbakhsh1, Sina Mojaverrostami1
1Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Central nervous system (CNS) lesions can repeatedly be de-and remyelinated during demyelinating diseases such as multiple sclerosis (MS). Here, we designed an intermittent demyelination model by 0.3 % Cuprizone feeding in C57/BL6 mice followed by two weeks recovery. Histochemical staining of luxol fast blue (LFB) was used for study of remyelination, detection of glial and endothelial cells was performed by immunohistochemistry staining for the following antibodies: anti Olig2 for oligodendrocyte progenitor cells, anti APC for mature oligodendrocytes, anti GFAP for astrocytes, and anti Iba-1 for microglia/macrophages, anti iNOS for M1 microglia/macrophage phenotype, anti TREM-2 for M2 microglia/macrophage phenotype and anti CD31 for endothelial cells. Also, real-time polymerase chain reaction was performed for assessment of the expression of the targeted genes. LFB staining results showed enhanced remyelination in the intermittent cuprizone (INTRCPZ) group, which was accompanied by improved motor function, increased mature oligodendrocyte cells, and reduction of astrogliosis and microgliosis. Moreover, switching from M1 to M2 polarity increased in the INTRCPZ group that was in association with downregulation of pro-inflammatory and upregulation of anti-inflammatory genes. Finally, evaluation of microvascular changes revealed a remarkable decrease in the endothelial cells in the cuprizone (CPZ) group which recovered in the INTERCPZ group. The outcomes demonstrate enhanced myelin content during recovery in the intermittent demyelination model which is in association with reshaping macrophage polarity and modification of glial and endothelial cells.
Insights
This study shows that intermittent demyelination and recovery in mice enhances myelin repair. This process involves shifting immune cells towards a healing state and improving motor function.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Demyelinating diseases like multiple sclerosis involve repeated myelin damage and repair.
- Understanding remyelination mechanisms is crucial for developing new therapies.
Purpose of the Study:
- To investigate the effects of an intermittent demyelination model on central nervous system (CNS) repair.
- To analyze the cellular and molecular changes associated with enhanced remyelination.
Main Methods:
- A mouse model of intermittent demyelination using Cuprizone was established.
- Remyelination was assessed using Luxol fast blue staining.
- Immunohistochemistry was used to detect glial cells, microglia/macrophages, and endothelial cells.
- Gene expression was analyzed using real-time polymerase chain reaction.
Main Results:
- Intermittent Cuprizone treatment led to enhanced remyelination and improved motor function.
- Increased mature oligodendrocytes and reduced glial scarring were observed.
- Macrophage polarization shifted from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes.
- Microvascular changes, including endothelial cell numbers, were modulated during recovery.
Conclusions:
- Intermittent demyelination followed by a recovery period promotes significant myelin repair in the CNS.
- The enhanced remyelination is linked to macrophage repolarization and glial cell modulation.
- This model provides insights into the cellular mechanisms underlying CNS repair in demyelinating conditions.
