Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth

International Journal of Molecular Sciences, 2014 · DOI: 10.3390/ijms151119535 · Published: October 28, 2014

Regenerative Medicine Neurology Genetics

Simple Explanation

This study investigates a surgical approach for ventral root avulsion (VRA), which results in motoneuron protection, combining it with bone marrow mononuclear cells (MC) therapy to see if nerve regeneration and synaptic recovery can be improved. The results indicated a significant preservation of inhibitory pre-synaptic boutons in the groups repaired with sealant alone and associated with MC therapy. The data demonstrate that root reimplantation at the lesion site may be considered a therapeutic approach and that MC therapy does not further improve the regenerative recovery, up to 12 weeks post lesion.

Study Duration

12 weeks

Participants

30 adult female Lewis rats

Evidence Level

Not specified

Key Findings

1
Root reimplantation preserves synaptic inputs, as shown by ultrastructural analysis of the spinal cord, leading to a close to normal synaptic covering compared to the avulsed group.
2
Ventral root avulsion leads to a preferential loss of excitatory terminals, creating an imbalance between inhibitory and excitatory synapses; reimplantation helps preserve spinal circuits.
3
Root reimplantation promotes axonal regeneration, allowing growth up to the target muscles, confirmed by an increased number of axons at 12 weeks after reimplantation compared to avulsion without reimplantation.

Research Summary

The study aimed to evaluate whether combining ventral root reimplantation with bone marrow mononuclear cell (MC) therapy could improve long-term nerve regeneration and synaptic recovery after ventral root avulsion (VRA). The findings demonstrated that root reimplantation alone significantly improved synaptic stability and axonal regeneration, but the addition of MC therapy did not provide further regenerative benefits in the long-term (12 weeks post-lesion). The results suggest that while root reimplantation is a promising therapeutic approach for CNS/PNS interface lesions, MC therapy may need to be repeated to sustain its short-term positive effects.

Practical Implications

Therapeutic Approach

Root reimplantation at the lesion site can be considered a therapeutic approach following proximal lesions in the interface of the CNS and PNS.

Limited MC Therapy Benefit

Mononuclear cell therapy does not further improve regenerative recovery up to 12 weeks post lesion.

Fibrin Sealant Potential

Fibrin sealant derived from snake venom can be used to repair proximal CNS/PNS lesions.

Study Limitations

1
The study only evaluated the effects of MC therapy up to 12 weeks, which may not be sufficient to observe long-term benefits.
2
The lack of significant differences with MC therapy in the long-term analysis does not necessarily mean that cell therapy is not effective.
3
The study was conducted on female Lewis rats, and the results may not be generalizable to other populations or species.

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