Tracking the evolution of CNS remyelinating lesion in mice with neutral red dye

PNAS, 2019 · DOI: 10.1073/pnas.1819343116 · Published: June 24, 2019

Simple Explanation

This study introduces a new method using neutral red (NR) dye to label and track demyelinating lesions in the central nervous system (CNS) of mice. The dye is injected into mice, and it specifically stains the demyelinated areas, allowing researchers to easily identify and dissect these lesions for further analysis. This technique enables detailed examination of molecular, cellular, and metabolic changes within the lesion microenvironment during remyelination, which could lead to the development of new therapies for demyelinating disorders like multiple sclerosis.

Study Duration

5, 10, and 20 d postlesion

Participants

C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
Neutral red (NR) dye effectively labels demyelinated lesions in the CNS of mice in both lysolecithin- and EAE-induced demyelination models.
2
NR-labeled lesions can be selectively dissected from unfixed CNS tissues for various analyses, including RT-qPCR, Western blot, flow cytometry, and mass spectrometry.
3
Metabolomic analysis of NR-labeled lesions revealed significant changes in amino acid and metabolite levels during demyelination and remyelination.

Research Summary

The study introduces a method to label CNS demyelinating lesions using neutral red (NR) dye, enabling easy identification and dissection of lesions. NR labeling allows for comprehensive analysis of molecular, cellular, and metabolic changes within the lesion microenvironment during remyelination. The findings can be used to identify molecular pathways that promote CNS repair and develop therapies to modulate neuroinflammation or enhance regeneration in demyelinating disorders.

Practical Implications

Enhanced Lesion Analysis

NR labeling allows for precise and efficient isolation of lesions for downstream analyses, improving the accuracy and depth of research.

Therapeutic Development

Identification of key molecular and metabolic pathways can facilitate the development of targeted therapies for demyelinating diseases.

Drug Screening

The NR labeling method can be applied to drug studies in EAE and other models to assess the effectiveness of immunomodulatory treatments.

Study Limitations

1
The diffuse nature of lesions in severe EAE models may pose challenges for isolating individual NR-labeled lesions.
2
The wide excitation and emission spectrums of NR have to be considered for colocalization studies to avoid cross-talk between fluorescent probes.
3
Future studies are needed to confirm whether NR-labeling correlates with lesion size under various treatment strategies.

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