Abstract
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. Fibroblast growth factor 2 (FGF-2) plays an important role in different processes such as neural induction, neuronal progenitor proliferation and their differentiation. Studies had shown an over expression of this growth factor after tail amputation. Nestin, a protein specific for intermediate filaments, is considered an early marker for neuronal precursors. It has been recently shown that its expression increases after tail transection in urodeles. Using this marker and western blots, our results show that the number of FGF-2 and FGFR2 mRNAs increases and is correlated with an increase in neurogenesis especially in the central canal lining cells immediately after lesion. This study also confirms that spinal cord re-growth through the lesion site initially follows a rostrocaudal direction. In addition to its role known in neuronal differentiation, FGF-2 could be implicated in the differentiation of ependymal cells into neuronal progenitors.
Highlights
It was in the late 1990s that scientists started to gather interesting information about urodeles
Nestin was expressed mainly in the rostral stump around the central canal. This implies that regeneration started in the anterior portion of the spinal cord (Ant SC: the pre-lesional stump) right after transection preceding the posterior portion (Post SC), in which nestin is still faint at 1 week after the operation
Retention of embryonic character is cited as a property that supports this regeneration process (Chernoff, 1996), but it is not clear to what extent embryonic processes involved in the central nervous system (CNS) development is retained or re-expressed
Summary
It was in the late 1990s that scientists started to gather interesting information about urodeles. These animals were found to be best suited to study regeneration because they are easy and inexpensive to maintain and breed in the laboratory. Microsurgery is simple, wound healing is rapid and requires very few sutures, and a minimal post-operative care is required. Morbidity and mortality are low and results are obtained relatively fast. Their tissues are easy to harvest and process for histological or immuno-cytochemical staining or molecular analysis. Known mammalian regenerative mechanisms in situ include compensatory hyperplasia (such as in the case of liver and pancreas), and activation of resident stem cells, but not dedifferentiation or trans-differentiation. Neurogenic ability in most regions of the central nervous system (CNS) is very limited (Goldman, 2004) and the production of new neurons is demonstrated to be almost arrested in adulthood (Hegedus et al, 2007)
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