Strategies for regenerating injured axons after spinal cord injury – insights from brain development

Masaki Ueno, Toshihide Yamashita

Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan

Abstract: Axonal regeneration does not occur easily after an adult central nervous system (CNS) injury. Various attempts have partially succeeded in promoting axonal regeneration after the spinal cord injury (SCI). Interestingly, several recent therapeutic concepts have emerged from or been tightly linked to the researches on brain development. In a developing brain, remarkable and dynamic axonal elongation and sprouting occur even after the injury; this finding is essential to the development of a therapy for SCI. In this review, we overview the revealed mechanism of axonal tract formation and plasticity in the developing brain and compare the differences between a developing brain and a lesion site in an adult brain. One of the differences is that mature glial cells participate in the repair process in the case of adult injuries. Interestingly, these cells express inhibitory molecules that impede axonal regeneration such as myelin-associated proteins and the repulsive guidance molecules found originally in the developing brain for navigating axons to specific routes. Some reports have clearly elucidated that any treatment designed to suppress these inhibitory cues is beneficial for promoting regeneration and plasticity after an injury. Thus, understanding the developmental process will provide us with an important clue for designing therapeutic strategies for recovery from SCI.

Keywords: development, regeneration, spinal cord injury