Spinal cord damage

Abstract

For decades, the irreversible functional loss following central nervous system injury has been perceived with a high degree of pessimism, and researchers challenging this assumption have been considered either heroic figures, or misguided fanatics. This high degree of pessimism regarding recovery evolved - in part - from many assumptions, among which that repair in the central nervous system (CNS) was likely to obey rules different from those governing wound healing or the repair of tissues outside the CNS. Therefore, it is not surprising that many phenomena, which were observed at the site of CNS injury and take part in the repair process outside the CNS, were believed to contribute to the failure of CNS repair and were therefore considered targets for elimination; these include the key processes of local inflammation and scar formation. In addition, the common manner in which the blood-brain barrier and the blood-cerebrospinal barriers were perceived led to the assumed linkage between brain pathologies and inflammation. Accordingly, it was believed that the CNS optimally functions and repairs itself in isolation from any circulating immune cells and has no need for assistance from peripheral immune cells to support repair; if immune cells infiltrate to the CNS territory, this was taken as a sign of pathology that should be mitigated. Nevertheless, through intensive studies over the last decade, many of these assumptions were challenged or modified. It became clear that the local immune response, encompassing activated microglia and infiltrating circulating immune cells, and scar formation are interim processes that are pivotal for overall repair, but require timely resolution. In addition, it became clear that resident microglia and infiltrating blood macrophages have distinct attributes and roles under pathological conditions; it is the timing and location of their activity that determine the outcome of their function. Furthermore, the requirements for neuronal rescue, protection, restoration, renewal, and regeneration differ in time, location, and the molecular and cellular players involved. According to this new development in the field of CNS injuries, the failure of recovery is not due to the occurrence of inflammation and scar formation, which are essential, but rather due to their insufficient timely resolution. This chapter will provide a historical perspective of the field, describe the emerging new understandings, and discuss their implications to therapies for spinal cord injury.