ABSTRACT Following injury, severed axons in the adult mammalian central nervous system (CNS) fail to regenerate beyond the lesion site. However, adult CNS neurons still have an intrinsic capability to regenerate axons if provided with an appropriate environment. Injury to the CNS induces tissue damage, which is repaired through wound healing processes that finally result in forming barriers to regeneration. Elimination of these barriers promotes axonal regeneration with only partial functional recovery. This indicates that eliminating the barriers is insufficient to promote robust axonal regeneration. In contrast to the adult CNS, robust axonal regeneration can occur beyond the lesion site in young animals, in which immature astrocytes play a key role to facilitate axonal regeneration. Thus, immature astrocytes appear to reconstruct the lost guidance cues at the lesion site in young animals. On the other hand, transplantation of Schwann cells, olfactory ensheathing cells, marrow stromal cells, astrocytes, fetal CNS tissue, and peripheral nerve grafts has been shown to induce axonal regeneration in adult CNS. However, accurate reconstruction of neural connections is essential for significant functional recovery, which requires the reconstruction of proper guidance cues at the lesion site. Within these strategies, transplantation of immature astrocytes or fetal CNS tissue is most likely to reconstruct the proper guidance cues at the lesion site and to induce the robust axonal regeneration with remarkable functional recovery.
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