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

Journal

EXPERIMENTAL NEUROLOGY
Volume 341, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2021.113704

Keywords

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

Categories

Funding

  1. Paralyzed Veterans of America: Research Foundation Grant
  2. Ontario Graduate Scholarship
  3. National Sciences and Engineering Research Council: Undergraduate Summer Research Award
  4. NIHNational Institutes of Neurological Disorders [R01 NS083942, R01 NS099532, R35NS111582]

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Spinal cord injury has complex pathophysiology, with neuroinflammation playing a major role in secondary injury. The use of systemic immunosuppressants is the primary pharmacological treatment, but its impact is complex, prompting the need for a superior approach. Comprehensive understanding of neuroinflammation and systemic immune responses is crucial for improving treatment methods.
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

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