CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 |Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept

Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is ascribed allegedly to immaturity, which has failed to be shown. The emergence of stem cells and their effective medical applications has intensified regeneration research into the spinal cord. However, despite these advances, the impact of clinical trials involving spinal cord-injured (SCI) patients remains disappointingly low. Long-distance regeneration has yet to be proven. Our study involving dorsal myelotomy in fetal rats examined the development of pioneering afferent axons during early gestation. We identified a critical period in the development of the long primary afferent system. A single cut demonstrated the intrinsic ability of these axons to regenerate toward their original targets in the spinal medulla. Compared to intact parent axons, we observed hypoxia-induced phenotypic changes in the severed fibers, making them distinctly recognizable life-long. This provides a tool for intrauterine reprogramming of dorsal root ganglion (DRG) neurons, as illustrated by various stills throughout the developmental progression of central axons. These axons' inferred high growth speed indicates a plausible missing link in CNS regeneration research. This paradigm could revolutionize preclinical research on CNS regeneration for SCI patients.