Neuroimmunological therapies for treating spinal cord injury: Evidence and future perspectives

Abstract

Spinal cord injury (SCI) has a complex pathophysiology. Following the initial physical trauma to the spinal cord, which may cause vascular disruption, hemorrhage, mechanical injury to neural structures and necrosis, a series of biomolecular cascades is triggered to evoke secondary injury. Neuroinflammation plays a major role in the secondary injury after traumatic SCI. To date, the administration of systemic immunosuppressive medications, in particular methylprednisolone sodium succinate, has been the primary pharmacological treatment. This medication is given as a complement to surgical decompression of the spinal cord and maintenance of spinal cord perfusion through hemodynamic augmentation. However, the impact of neuroinflammation is complex with harmful and beneficial effects. The use of systemic immunosuppressants is further complicated by the natural onset of post-injury immunosuppression, which many patients with SCI develop. It has been hypothesized that immunomodulation to attenuate detrimental aspects of neuroinflammation after SCI, while avoiding systemic immunosuppression, may be a superior approach. To accomplish this, a detailed understanding of neuroinflammation and the systemic immune responses after SCI is required. Our review will strive to achieve this goal by first giving an overview of SCI from a clinical and basic science context. The role that neuroinflammation plays in the pathophysiology of SCI will be discussed. Next, the positive and negative attributes of the innate and adaptive immune systems in neuroinflammation after SCI will be described. With this background established, the currently existing immunosuppressive and immunomodulatory therapies for treating SCI will be explored. We will conclude with a summary of topics that can be explored by neuroimmunology research. These concepts will be complemented by points to be considered by neuroscientists developing therapies for SCI and other injuries to the central nervous system.

Keywords: Adaptive immune response; Blood-spinal cord-barrier; Immune organs; Immunomodulation; Immunosuppression; Innate immune response; Neuroimmunology; Neuroinflammation; Spinal cord injury.