Translational perspective

The last three decades have witnessed transformative advances in biology and neuroscience. Still, regeneration of axons after traumatic spinal cord injury (SCI) remains a significant medical challenge and need. The central nervous system has a limited capacity for endogenous repair as compared to other tissues such as nerve, bone, skin, and liver. Key knowledge areas contributing to the multidisciplinary field of neuroregeneration therapeutics include molecular and developmental neurobiology, stem cell and peripheral nerve biology, experimental neuropathology, neurophysiology, and biomedical and materials engineering. Key experimental techniques include cell culture, microfluidics, high-throughput screening, animal modeling, and human clinical trials. This chapter reviews key concepts with a particular view of the field's evolution, what has been tested in people with SCI, and what therapeutic applications seem feasible in the near future to accomplish more effective regeneration. We briefly describe some unifying key molecular pathways as currently understood, such as PTEN inhibition of the PI3K–Akt–mTOR pathway, and while we emphasize specific interactions such as reducing axonal growth inhibition, few of the molecules discussed have only one activity. The reader is referred to online resources such as the Kegg Pathway database (https://www.genome.jp/kegg/pathway.html) for greater detail and omics integrated systems analyses focused on SCI.