Ca2+-induced myelin pathology precedes axonal spheroid formation and is mediated in part by store-operated Ca2+ entry after spinal cord injury

Neural Regeneration Research, 2023 · DOI: https://doi.org/10.4103/1673-5374.373656 · Published: April 10, 2023

Simple Explanation

This study investigates how calcium affects nerve fiber damage after spinal cord injury. It focuses on axonal spheroids, a common sign of damage. The researchers used a mouse spinal cord model to observe how calcium release from internal stores and entry from outside the cell contribute to myelin and axon damage. They found that releasing calcium from internal stores leads to myelin damage first, followed by axonal spheroid formation, and that store-operated calcium entry (SOCE) plays a key role in this process.

Study Duration

Not specified

Participants

Adult 6–8-week-old transgenic mice

Evidence Level

Ex vivo study

Key Findings

1
Ionomycin dose-dependently induces pathological changes in myelin and pronounced axonal spheroid formation.
2
Periaxonal swelling is an early event after ionomycin treatment followed by the gradual formation of axonal spheroids.
3
Inhibition of store-operated Ca2+ entry significantly reduced myelin ring formation.

Research Summary

This study investigates the role of calcium in myelin and axonal degeneration following spinal cord injury, using an ex vivo mouse spinal cord model. The findings indicate that ionomycin-induced release of calcium from internal stores leads to initial myelin damage (periaxonal swelling) followed by axonal spheroid formation. The study identifies store-operated calcium entry (SOCE) as a major route for external calcium entry contributing to both myelin and axonal pathology, suggesting SOCE as a potential therapeutic target.

Practical Implications

Therapeutic Target Identification

Store-operated calcium entry (SOCE) is identified as a potential therapeutic target to protect myelinated fibers after spinal cord injury.

Understanding SCI Pathology

The study provides insights into the temporal sequence of events in SCI, with myelin damage preceding axonal spheroid formation.

Calcium's Role Elucidated

The research clarifies the distinct roles of internal calcium stores and external calcium entry in the progression of SCI-related damage.

Study Limitations

1
Lack of blood-derived elements in the ex vivo model.
2
Chemical versus mechanical injury-induced axonal spheroid formation.
3
Limited viability of ex vivo models compared to the protracted period of secondary white matter degeneration in vivo.

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