Molecular mechanisms that promote or inhibit axon growth have being studied, using various injury paradigms, in different neuronal types and species. Some species have poor central regeneration, whereas others have the capacity to regenerate. Axons in the peripheral nervous system of mammals also show extensive regeneration. The review by Martin Oudega of the University of Pittsburgh provides a comprehensive discussion comparing the molecular mechanisms found in mammals and zebrafish. These comparisons allow for a better understanding of the underlying principles. Remarkably, regeneration in the zebrafish central nervous system is also incomplete. Some axon tracts can regenerate but others cannot. This makes zebrafish an interesting model system for spinal cord injury research along with the traditional mammalian models such as rats and mice. Feng-Quan Zhou of Johns Hopkins Medical School discusses signaling mechanisms that lead to axon regeneration in the mammalian peripheral nervous system, in Drosophila and in Caenorhabditis elegans. Jeff Twiss of the University of South Carolina contributes an original paper reporting that protein translation machinery is present in the peripheral branches of the axons of mammalian dorsal root ganglion cells, which can regenerate, suggesting that the capacity of local protein thesis is essential for regeneration.

The glial scar presents strong inhibitory cues for regeneration, an influence that still needs to be overcome. At the same time, the glial scar provides a barrier against inflammation to limit secondary injury, and this is beneficial. Chen He of the Second Military Medical University (Shanghai) discusses the complex role of the glial scar in influencing axon regeneration and neuroinflammation. The choice of appropriate experimental systems and species for spinal cord injury research is crucial. Jae Lee of the University of Miami provides a comprehensive discussion of different experimental systems for spinal cord injury, animal species, and lesion paradigms.

Injury can cause neuronal loss, so keeping neurons alive is of high priority. Gong Ju of the Fourth Military Medical University (Xi’an) contributes an original research article on the role of Batroxobin in protecting neurons, which may have therapeutic potential. Qiang Liu of the First Clinical Medical College of Shanxi Medical University (Taiyuan) reports that valproate reduces autophagy and promotes neuroprotection.

Many improvements of locomotor function have been attributed to axons that regenerate across the lesion site. Wutian Wu of the University of Hong Kong contributes an original research article showing that sometimes such functional improvement may be unrelated to the regeneration of these particular axons. He proposes that adaptation of neural circuits in the spinal cord below the transaction site may contribute to improved function, suggesting that the circuitry in the spared tissue has adaptive potential that we may not have appreciated.

Jean-Marie Cabelguen of the University of Bordeaux summarizes insights from studies of lower vertebrates that have an extensive capacity for regeneration and functional recovery in the central nervous system. However, even in the salamander, regeneration is imperfect. The number of axons achieving correct innervation is less than normal and regenerated axons can innervate inappropriate targets in transected animals. Interestingly, neither new brainstem neurons (neurogenesis) nor axon collaterals from unlesioned neurons (sprouting) contribute to the restoration of descending projections after spinal cord transection in salamanders, fish, and larval lampreys. This suggests that plasticity is limited in this sense. In turtles, even when regeneration of axons does occur, functional recovery is incomplete (limited to stepping). This suggests that even if we achieve massive regeneration of central nervous system axons in mammals, we may still face the issues of the extent of regrowth and correct targeting for functional recovery, which require a better understanding of the mechanisms of axon growth and guidance. In the completely transected fish and cat, daily training can result in functional recovery, suggesting that sensory afferents play crucial roles in reactivating the locomotor central pattern generator. This is potentially consistent with the findings reported by Wutian Wu in this issue.

Studies in some areas of spinal cord injury research have entered the phase of actively developing therapeutic approaches. James Fawcett of the University of Cambridge summarizes work centered around combinatorial treatment with Chondrotinase ABC and other approaches to achieve regeneration based on progress in molecular signaling in glial scar inhibition. Riyi Shi of Purdue University discusses an interesting tissue-engineering approach using polyethylene glycol, which reseals membrane and repairs mitochondria to reduce oxidative stress and minimize secondary injury. Agnes Haggerty of the University of Pittsburgh covers promising biomaterials for the repair of damaged spinal cord. These exciting efforts will help accelerate translational research in the field of spinal cord injury.

The success of spinal cord injury repair depends on multidisciplinary approaches that address multiple aspects of injury responses. More robust axon regeneration with proper guidance and synapse formation are the ultimate goals for restoring maximal function. This will probably most effectively be done in combination with functional rehabilitation. Effective neuroprotective agents will enhance success in the long-term and should be included in the care package. Better understanding of the neural circuit functions controlling sensory-motor behaviors will provide more sophisticated molecular and rehabilitation designs. Using proper animal models for preclinical studies will also help identify promising therapies. A more severe and rapidly growing condition, traumatic brain injury, poses ever-increasing challenges. Even less is known about traumatic brain injury. It is conceivable that these two areas of research will have more and more active interactions in the future.

More information is available at http://www.neurosci.cn or http://www.springer.com/biomed/neuroscience/journal/12264.