Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

Journal of Visualized Experiments, 2016 · DOI: doi:10.3791/54348 · Published: September 12, 2016

Simple Explanation

Multiple sclerosis (MS) involves immune cells attacking the brain and spinal cord, leading to myelin destruction and nerve damage. Current treatments aim to reduce immune cell infiltration into the central nervous system (CNS). This protocol helps determine if a drug protects the CNS either by reducing immune cell infiltration or by preventing the death of CNS cells during inflammatory events. The method uses animal models of MS (EAE) and combines flow cytometry with immunohistochemistry to analyze the effects of therapies on immune cell proliferation, infiltration, and CNS protection.

Study Duration

Not specified

Participants

Mice (C57BL/6 and SJL)

Evidence Level

Not specified

Key Findings

1
The protocol differentiates between treatments that suppress the immune system and those that directly protect the CNS during autoimmune demyelination.
2
Using different EAE models (C57BL/6 and SJL mice), the study assesses the impact of therapeutic agents on immune cell infiltration into the spinal cord and brain, respectively.
3
Flow cytometry and immunohistochemistry are used to quantify immune cell populations and assess the extent of neuroinflammation and myelin preservation.

Research Summary

The study presents a protocol to differentiate between immune system suppression and CNS protection for pharmacological interventions in autoimmune demyelination. It utilizes EAE models in mice, combined with flow cytometry and immunohistochemistry, to assess the effects of treatments on immune cell infiltration, proliferation, and CNS damage. The protocol helps researchers determine if a drug protects the CNS by reducing immune cell infiltration or by directly preventing CNS cell death, aiding in the development of more effective MS therapies.

Practical Implications

Drug Development

This method assists researchers in identifying and developing drugs that specifically target CNS protection, leading to more effective MS treatments.

Understanding MS Pathogenesis

The protocol provides a framework to better understand the interactions between the immune system and CNS in the context of autoimmune demyelination.

Clinical Trial Design

The findings can inform the design of clinical trials by helping to identify appropriate treatment windows and outcome measures for assessing neuroprotective effects.

Study Limitations

1
Immune cells may enter the CNS but be unable to travel in the parenchyma.
2
The microbiome can heavily influence EAE pathogenesis.
3
The effects of immune cell proliferative changes in the periphery may influence the results.

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