Editorial: Karolinska Institutet 200-Year Anniversary Symposium on Injuries to the Spinal Cord and Peripheral Nervous System—An Update on Recent Advances in Regenerative Neuroscience

摘要

Editorial on the Research Topic Karolinska Institutet 200-Year Anniversary Symposium on Injuries to the Spinal Cord and Peripheral Nervous System—An Update on Recent Advances in Regenerative Neuroscience The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nerves in 2010 gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury fields, covering topics from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation ( Skold et al. ). The present Research Topic recognizes the remarkable advances in regenerative neuroscience that have occurred over the past years.In this Research Topic, we are pleased to present contributions from basic laboratory studies to new clinical strategies in the spirit of highlighting advancements in regenerative neuroscience and functional repair of traumatic injuries to the spinal cord and peripheral nerves.As the main conduits of information from the periphery to the brain and vice versa, the spinal cord and the spinal nerves are of fundamental importance. The location of spinal motor and sensory neurons within both the central and peripheral nervous systems, with profoundly different responses to nerve injury, make these neurons especially interesting for understanding fundamental aspects of nerve injury and regeneration.In injuries to the spinal cord, the primary injury results in damage of cells, extracellular matrix, and vasculature, that in turn give rise to a secondary injury cascade with consequent ischemia, inflammation, and death of glial cells and neurons. Formation of glial scars and cystic cavities are the result of posttraumatic changes in the structural architecture of the posttraumatic spinal cord which are of importance for the capacity of regrowth of axons, the poor recovery potential and resulting neurological capacity.The glial scar is formed in a dynamic process after injury to the spinal cord and its potentially inhibitory as well as supportive effect on nerve regrowth has been studied widely ( 1 – 4 ).In the zone around the lesion, activated astrocytes, microglia, invading macrophages, and fibroblast are arranged together with secreted extracellular matrix molecules to form the glial scar. Myelin forming oligodendrocytes are commonly lost after spinal cord injuries leaving axons demyelinated ( 5 ) while surviving and new oligodendrocytes may not contribute to effective functional remyelination ( 6 , 7 ). On the other hand, it is well known that oligodendrocyte progenitor cells, the so-called NG2 cells, do migrate to the spinal cord lesion and probably play a multifold function therein; secreting nerve growth inhibitory ECM molecules (chondroitin sulfate proteoglycans) and differentiating to myelin-producing oligodendrocytes and even astrocytes, although much of their function remains elusive. In the contribution to this Research Topic by Hackett and Lee , we do get a comprehensive review on NG2 cells and their role in health and disease. Hackett et al. point out that NG2 cells are, besides astrocytes, one major part of the glial scar. However, unlike astrocytes, they can differentiate into oligodendrocytes, astrocytes, and perhaps even Schwann cells and, thus, be a target in many aspects of spinal cord injury and repair.Even though lack of nerve regeneration, or at least successful nerve regeneration, is the rule after injuries to the central nervous system (CNS), endogenous mechanisms and exceptions to this dogma of unsuccessful nerve regeneration do exist and hold promise of a wider understanding of how, when, and where nerve regeneration can occur and be supported. Anatomical and synaptic plasticity ( 8 ) as well as activation and development of neural precursor cells in to neurons and glia ( 9 ) after spinal cord injury are endogenous reparative attempts that need further exploration.One interesting example of successful CNS nerve regeneration is the avulsion-replantation injury of spinal nerves ( Carlstedt ). When spinal roots, typically in high velocity traffic accidents, are torn from the spinal cord, this results in an interruption of the local transverse segmental spinal cord motor and sensory fibers. This will lead to dying back of the centrally located axon and, eventually, the motor neuron in the ventral horn of the spinal cord. However, if the avulsed spinal root is replanted to the spinal cord, survival of motor neurons and successful regeneration of axons from the motor neurons within the CNS will occur ( 10 ), which has resulted in a surgical method to restore function after this kind of longitudinal spinal cord injury ( 11 ).In his perspectives article, Carlstedt elaborates on recent findings regarding the return of sensory function. Replantation of avulsed spinal roots leads to useful motor function if the procedure is performed before 1?month after injury ( 12 ), but sensory recovery cannot be achieved by replanting avulsed do