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Updated: Apr 2, 2026
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Cell death of spinal cord ED1(+) cells in a rat model of multiple sclerosis
Dragana Trifunović1, Neda Djedović2, Irena Lavrnja3
1Institute for Ophthalmic Research, University of Tuebingen , Tuebingen , Germany.
Abstract:
Infiltration of macrophages into the central nervous system and activation of microglia are hallmarks of multiple sclerosis and its animal model-experimental autoimmune encephalomyelitis (EAE). Cell death in EAE has been demonstrated as an essential mechanism in the local regulation of the inflammatory reaction, but also as one of the major factors contributing to the destruction of the nervous tissue. The focus of this study was on detection of cell death among ED1(+) cells (macrophages/activated microglia) in the spinal cord of Dark Agouti rats at the peak of EAE. Cell death was assessed using the TUNEL assay and immunostaining for cleaved caspase 3, as markers for cell death in general and "classical" apoptosis, respectively. Major infiltrates of immune cells were detected both in white matter and gray matter of spinal cords in rats at the disease peak. ED1, TUNEL, and caspase 3 positive cells were detected within, but also outside the infiltrates. There were more dying ED1(+) cells in white matter than in gray matter, both in the general population and in infiltrated regions. The observed discrepancy in the proportion of dying ED1(+) cells in spinal cord gray and white matter indicated that in EAE rat macrophages/microglia within gray matter are less prone to cell death induction. This is of special interest in the context of the increasingly appreciated contribution of spinal cord gray matter inflammation to multiple sclerosis pathogenesis. Our findings suggest that activated macrophages/microglia of gray matter are less susceptible to cell death induction. Alternatively, it can be assumed that intrinsic cell death-inductive mechanisms of nervous tissue differ in white and gray matter. Thus, further research on the gray matter macrophages/microglia cell death during EAE is warranted. They should be aimed at identification of the reasons for the observed differences and finding suitable ways to stimulate gray matter activated macrophages/microglia death.
Insights
In experimental autoimmune encephalomyelitis (EAE), dying macrophages/microglia were more prevalent in white matter than gray matter of the spinal cord. This suggests gray matter immune cells are less susceptible to cell death during central nervous system inflammation.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Macrophages and microglia activation are key features of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).
- Cell death in EAE regulates inflammation and contributes to nervous tissue destruction.
Purpose of the Study:
- To detect cell death in ED1-positive cells (macrophages/activated microglia) within the spinal cord of Dark Agouti rats at the peak of EAE.
- To investigate differences in cell death rates between gray and white matter macrophages/microglia during EAE.
Main Methods:
- Utilized TUNEL assay and immunostaining for cleaved caspase-3 to identify cell death.
- Examined spinal cords from rats at the peak of EAE, focusing on ED1-positive cells.
Main Results:
- Significant immune cell infiltrates were observed in both white and gray matter of the spinal cord.
- Dying ED1-positive cells were found both within and outside immune infiltrates.
- A higher proportion of dying ED1-positive cells was detected in white matter compared to gray matter.
Conclusions:
- Macrophages/microglia in the gray matter of EAE rat spinal cords exhibit reduced susceptibility to cell death induction.
- This differential cell death rate may indicate distinct intrinsic mechanisms of cell death regulation in gray versus white matter.
- Further research is needed to understand the reasons for these differences and explore methods to induce gray matter macrophage/microglia death in EAE.
