An update on spinal cord injury research

Abstract

Spinal cord injury (SCI) is an ever-increasing challenge.Severe injury can cause long-term loss of sensory and motor functions, as well as other chronic conditions, such as neuropathic pain and autonomic dysreflexia. So far, most research has been focused on acute injury. However, due to the lack of treatment, more and more individuals with this condition enter a chronic state, to which very little research effort has been dedicated. SCI is a complex condition. It involves damage to axons, death of neurons, neuroinflammation, glial scar formation, loss of myelin, and lack of remyelination. It is clear that effective treatment will require combinatorial approaches. The 12 invited articles for this special issue on SCI provide an update on many of these areas of SCI research. Here, I highlight the articles and reviews by theme.Severe SCI involves severing of axons, breaking ascending and descending connections. Inhibitory molecules in the environment of the adult central nervous system, such as the myelin-associated inhibitors and proteoglycans in glial scars, were thought to be the major cause of the lack of regeneration for many years [1] .However, efforts to regenerate axons across a lesion site in the mammalian spinal cord by overcoming this inhibition have not been successful. In some cases, axon regeneration into cell grafts can be achieved, as in studies using preconditioning lesion paradigms of sensory axons [2] .But few axons project beyond the lesion and reach longrange targets. In recent years, more attention has been shifted to enhancing the intrinsic growth capacity of adult central nervous system axons. Deletion of pTEN (phosphatase and tensin homolog) induces unprecedented regeneration across the fully-transacted spinal cord [3] .Neurons derived from embryos or induced pluripotent stem cells that have strong intrinsic growth properties can ignore inhibitory cues in the adult spinal cord and grow long distances up and down the cord [4] . In partial injury, rerouting and sprouting of axons result in circuit reorganization in the spared tissue and have been shown to be effective in restoring function using a combination of pharmacological and electrophysiological stimulation and robot-assisted rehabilitation techniques [5,6] . Molecular mechanisms that promote or inhibit axon growth have been 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 [7] 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 SCI research along with the ...

Mst‐1 deficiency promotes post‐traumatic spinal motor neuron survival via enhancement of autophagy flux

“…Spinal cord injury is a devastating condition causing paralysis and sensorimotor impairments, which consists of primary and secondary injury and their mechanisms has not been clearly stated yet (Zou ). The primary injury occurs simultaneously at the accident, leading to neuron death directly; whereas, the secondary injury is characterized by extensive and persistent pathological stress, including ischemia, oxidative stress, ionic homeostasis disturbances, and inflammatory responses.…”