Neurogenesis and growth factors expression after complete spinal cord transection in Pleurodeles waltlii

Frontiers in Cellular Neuroscience, 2015 · DOI: 10.3389/fncel.2014.00458 · Published: January 13, 2015

Neurology Regenerative Medicine & Stem Cells

Simple Explanation

Following spinal lesion, connections between the supra-spinal centers and spinal neuronal networks can be disturbed, which causes the deterioration or even the complete absence of sublesional locomotor activity. In mammals, possibilities of locomotion restoration are much reduced since descending tracts either have very poor regenerative ability or do not regenerate at all. However, in lower vertebrates, there is spontaneous locomotion recuperation after complete spinal cord transection at the mid-trunk level. This phenomenon depends on a translesional descending axon re-growth originating from the brainstem. On the other hand, cellular and molecular mechanisms underlying spinal cord regeneration and in parallel, locomotion restoration of the animal, are not well known. This study shows that the ependymal cells remained active, filled the gap between both spinal cord stumps and expressed nestin (intermediate filament marker), bFGF, one of its receptors (FGFR2) and neurofilament (NF, adult neurons marker).

Study Duration

24 weeks

Participants

25 urodele amphibians (Pleurodeles waltlii)

Evidence Level

Not specified

Key Findings

1
Nestin expression is prominent in the rostral part of the spinal cord next to the lesion site one week after transection, implying neuronal progenitor migration to replace the missing tissue.
2
Six weeks post-transection, nestin expression increases dramatically, cells become more organized, and both stumps connect at the transection site.
3
FGF-2 and FGFR2 mRNA expression increase after lesion, peaking at 15 weeks post-transection, then decreasing during locomotion recovery.
4
New neurons formed after spinal cord transection in urodele amphibians are oriented towards the lesion site, with ependymal cells being the major source of proliferative cells.

Research Summary

This study investigates spinal cord regeneration in Pleurodeles waltlii after complete transection, focusing on the role of neurogenesis and growth factors. It demonstrates that ependymal cells fill the gap between spinal cord stumps, expressing nestin, bFGF, and FGFR2, and that spinal cord re-growth follows a rostrocaudal direction. The study shows that nestin expression increases dramatically six weeks post-transection, cells become more organized, and both stumps of the lesioned spinal cord get connected at the transection site; replacing thus the gap created by the operation. The study concludes that after complete transection of the mid-trunk spinal cord, Nestin, FGF-2 and FGFR2 are gradually expressed throughout the regeneration process reaching a peak at 15 weeks after lesion concomitant with recovery of the locomotor activity.

Practical Implications

Understanding Spinal Cord Regeneration

Urodele spinal cord regeneration can make an important contribution by defining the requirements for successful CNS regeneration through experimental manipulation of a regenerating adult system that allows examination of the cell interactions that elicit regeneration.

Potential Therapeutic Strategies

Findings encourage the possibility that precursor cells from the human CNS may be used in cell replacement or gene therapy strategies directed toward human neurodegenerative disorders.

Ependymal Cell Role

Ependymal cells may become a buffer between the neurons and the processes that trigger secondary cell death and axonal degeneration.

Study Limitations

1
Experimental system limited to urodeles
2
Integration of molecular regulators of neurogenesis is still not fully understood.
3
Not specified

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