Spinal cord regeneration: where fish, frogs and salamanders lead the way, can we follow?

Major trauma to the mammalian spinal cord often results in irreversible loss of function, i.e. paralysis, and current therapies ranging from drugs, implantations of stem cells and/or biomaterials, and electrically stimulated nerve regrowth, have so far offered very limited success in improving quality-of-life. However, in marked contrast with this basic shortcoming of ours, certain vertebrate species, including fish and salamanders, display the amazing ability to faithfully regenerate various complex body structures after injury or ablation, restoring full functionality, even in the case of the spinal cord. Despite the inherently strong and obvious translational potential for improving treatment strategies for human patients, our in-depth molecular-level understanding of these decidedly more advanced repair systems remains in its infancy. In the present review, we will discuss the current state of this field, focusing on recent progress in such molecular analyses using various regenerative species, and how these so far relate to the mammalian situation. Abbreviations: BDNF, brain-derived neurotrophic factor; BMP, bone morphogenetic protein; CNS, central nervous system; CSPG, chondroitin sulfate proteoglycan; CST, cortico-spinal track; DLK, dual leucine zipper kinase; DRG, dorsal root ganglion (ganglia); E, embryonic day; ECM, extracellular matrix; FGF, fibroblast growth factor; GFAP, glial fibrillary acidic protein; GFP, green fluorescent protein; 5-HT, 5-hydroxytryptamine; JNK, c-Jun N-terminal kinase; MAG, myelin-associated glycoprotein; MAP, microtubule-associated protein; NgR, Nogo receptor; Nogo, neurite outgrowth inhibitor; OMgp, oligodendrocyte-myelin glycoprotein; OPC, oligodendrocyte precursor cell; PNS, peripheral nervous system; TH1, tyrosine hydroxylase 1