Forced Remyelination Promotes Axon Regeneration in a Rat Model of Spinal Cord Injury

Int. J. Mol. Sci., 2023 · DOI: 10.3390/ijms24010495 · Published: December 28, 2022

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injuries (SCI) result in the loss of motor and sensory functions controlled by neurons located at the site of the lesion and below. The study hypothesized that experimentally enhanced remyelination supports axon preservation and/or growth in the total spinal cord transection in rats. Multifocal demyelination was induced by injection of ethidium bromide (EB), either at the time of transection or twice during transection and at 5 days post-injury. The number of oligodendrocyte progenitor cells (OPCs) signiﬁcantly increased 14 days after demyelination. Behavioral tests revealed signiﬁcant improvement in locomotor function recovery in double-EB-injected rats, which was impaired by the blockade of serotonin receptors, conﬁrming the important role of restored serotonergic ﬁbers in functional recovery.

Study Duration

2–3 months

Participants

Adult female WAG rats

Evidence Level

Animal study

Key Findings

1
A signiﬁcant number of axons passed the injury epicenter and entered the distant segments of the spinal cord in the double-EB-injected rats. Moreover, some serotoninergic ﬁbers, not detected in control animals, grew caudally through the injury site.
2
Enhanced remyelination supports the regeneration of serotoninergic descending ﬁbers which, at least in part, promotes functional recovery.
3
Forced white matter remyelination promotes axonal regeneration in a rat model of spinal cord injury, enhancing OPC recruitment and differentiation, Schwann cell invasion/differentiation, and spontaneous axon growth throughout the transection site.

Research Summary

This study investigates the ability of forced remyelination to support axon regeneration in an acute and chronic total transection model using ethidium bromide (EB) to induce focal demyelination within the transected spinal cord. The results demonstrated that induced remyelination improves functional recovery after transection by enhancing oligodendrocyte precursor recruitment and differentiation, resulting in oligodendrocyte and Schwann-cell-mediated remyelination without substantial suppression of glial scar formation. The study postulates that enhancing remyelination early after traumatic insult could be permissive for axon survival and regrowth, leading to the preservation of hind limb functions in a rat model of complete spinal cord transection.

Practical Implications

Therapeutic Strategies

Mobilizing endogenous OPCs and/or Schwann cells to migrate into the injury site and enhance remyelination of the affected axons may substantially support their survival and ultimately locomotor recovery.

Pharmacological Promotion

Recent advances in understanding the complex mechanisms of remyelination and the potential of its modulation, achieved either by pharmacological promotion of endogenous OPC migration and subsequent differentiation, could be employed in spinal cord injury treatment.

Inflammatory Modulation

Modulating the inflammatory reaction could be also employed in spinal cord injury treatment.

Study Limitations

1
The study uses a rat model, which may not fully translate to human spinal cord injury.
2
The specific mechanisms underlying the role of remyelination in promoting serotonergic axon regeneration require further investigation.
3
The long-term effects of forced remyelination on spinal cord function were not extensively explored.

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