Remyelination reporter reveals prolonged reﬁnement of spontaneously regenerated myelin

PNAS, 2013 · DOI: 10.1073/pnas.1210293110 · Published: March 5, 2013

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how myelin, the protective coating around nerve fibers, regenerates after spinal cord injury. Researchers used a special mouse model that allows them to track newly formed myelin and distinguish it from existing myelin. The study found that newly regenerated myelin sheaths, initially shorter than normal, gradually lengthen over several months. Surprisingly, the thickness of the new myelin was often similar to that of existing myelin, challenging previous assumptions. These findings suggest that remyelination is a dynamic process and that our understanding of it has been limited by the inability to properly identify regenerated myelin. The study also showed that different types of cells, Schwann cells and oligodendrocytes, regenerate myelin on different sized nerve fibers.

Study Duration

6 Months

Participants

24 transgenic mice

Evidence Level

Level 2: Experimental study using a transgenic mouse model

Key Findings

1
OL-regenerated sheaths elongated progressively over 6 mo to approach control values.
2
OL-regenerated myelin thickness was not signiﬁcantly different from control myelin at most time points after injury.
3
SCs selectively ensheathed larger caliber axons, while OLs predominantly ensheathed smaller axons early after injury.

Research Summary

This study used a transgenic mouse model to visualize and quantify spontaneously regenerated myelin after spinal cord injury, distinguishing it from pre-existing myelin. The research challenges the assumption that regenerated myelin is always abnormally thin and short, revealing that OL-regenerated sheaths elongate over time and can achieve normal thickness. The study also demonstrates that Schwann cells and oligodendrocytes selectively remyelinate axons of different calibers, highlighting the complexity of the remyelination process.

Practical Implications

Rethinking Remyelination Assessment

The study suggests that morphological criteria alone are insufficient to assess the extent and quality of regenerated myelin, necessitating new methods for empirical categorization.

Targeted Therapies

Understanding the distinct roles of Schwann cells and oligodendrocytes in remyelination could lead to more targeted therapeutic strategies for demyelinating disorders.

Plasticity and Rehabilitation

The finding that remyelination can elongate independently of axonal growth highlights the potential for plasticity and suggests avenues for rehabilitation strategies to promote myelin refinement.

Study Limitations

1
Potential exclusion of membrane label from compact myelin structures over time.
2
Confocal analysis of myelin thickness may not give exact myelin measurements as seen by high-contrast EM.
3
The study focuses on a specific mouse model of spinal cord contusion injury, which may not fully represent the complexity of demyelination in other conditions.

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