LOTUS Inhibits Neuronal Apoptosis and Promotes Tract Regeneration in Contusive Spinal Cord Injury Model Mice

eNeuro, 2018 · DOI: https://doi.org/10.1523/ENEURO.0303-18.2018 · Published: October 22, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Following spinal cord injury (SCI), the body's natural ability to recover is limited. This is partly due to a protein called Nogo receptor-1 (NgR1), which inhibits the regrowth of nerve fibers. LOTUS, a substance that blocks NgR1, can help overcome this inhibition. This study used a clinically relevant spinal cord injury model in mice to test the therapeutic effects of LOTUS. The results showed that LOTUS promoted the regeneration of specific nerve tracts and protected nerve cells from dying. Overall, this research suggests that LOTUS could be a beneficial treatment for spinal cord injury. By promoting nerve regeneration and protecting nerve cells, LOTUS may help improve motor function and overall recovery.

Study Duration

56 days

Participants

LOTUS-Tg and C57BL/6J mice (eight-week-old, female, 18–22 g)

Evidence Level

Not specified

Key Findings

1
LOTUS overexpression reduced spinal cord atrophy and protected myelinated neuronal fibers against injury.
2
LOTUS promoted an increase in reticulospinal neurons that project axons caudal to the injury site.
3
LOTUS enhanced raphespinal tract regeneration by promoting translesional elongation of this tract.

Research Summary

The study evaluated the therapeutic benefits of LOTUS pan-neuronal overexpression in the injured spinal cord using a clinically relevant contusive SCI model. LOTUS has a neuroprotective effect on the spinal cord through reducing cellular apoptosis during the acute phase following SCI. LOTUS overexpression enhances neuronal protection, axonal regeneration and functional recovery after a more clinically relevant contusive SCI model.

Practical Implications

Therapeutic Strategy for SCI

LOTUS, with its strong inhibitory action against NgR1, may represent a therapeutic strategy for SCI by promoting endogenous restoration and locomotor improvement.

Clinical Relevance

The study utilized a contusive SCI model, which is more clinically relevant than transection models, enhancing the potential for translation to human treatments.

Nerve Conduction Improvement

LOTUS pan-neuronal overexpression potentially improves nerve conduction, as indicated by shorter MEP latency and larger MEP amplitude.

Study Limitations

1
Long-distance elongation of the CST was not observed beyond the edge of the caudal lesion site.
2
The mechanism by which NgR1 signaling affects cellular apoptosis after CNS injury is not fully understood.
3
Further studies of the phenotype and time course changes postinjury are needed to elucidate the regenerative effect of LOTUS on the reticulospinal tract.

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