Abstract
Spinal cord injury (SCI) is a devastating event that results in significant physical disabilities for affected individuals. Apart from local injury within the spinal cord, SCI patients develop a variety of complications characterized by multiple organ dysfunction or failure. These disorders, such as neurogenic pain, depression, lung injury, cardiovascular disease, liver damage, kidney dysfunction, urinary tract infection, and increased susceptibility to pathogen infection, are common in injured patients, hinder functional recovery, and can even be life threatening. Multiple lines of evidence point to pathological connections emanating from the injured spinal cord, post-injury systemic inflammation, and immune suppression as important multifactorial mechanisms underlying post-SCI complications. SCI triggers systemic inflammatory responses marked by increased circulation of immune cells and pro-inflammatory mediators, which result in the infiltration of inflammatory cells into secondary organs and persistence of an inflammatory microenvironment that contributes to organ dysfunction. SCI also induces immune deficiency through immune organ dysfunction, resulting in impaired responsiveness to pathogen infection. In this review, we summarize current evidence demonstrating the relevance of inflammatory conditions and immune suppression in several complications frequently seen following SCI. In addition, we highlight the potential pathways by which inflammatory and immune cues contribute to multiple organ failure and dysfunction and discuss current anti-inflammatory approaches used to alleviate post-SCI complications. A comprehensive review of this literature may provide new insights into therapeutic strategies against complications after SCI by targeting systemic inflammation.
Highlights
Spinal cord injury (SCI) causes disastrous damage to patients
While much consideration should be given to the brainstem’s role in multiple organ dysfunction following SCI, this review focuses on the contributive roles of inflammation and immunity in these systemic complications
Post-SCI multiple organ dysfunction is influenced by multifactorial mechanisms, and the extent to which systemic inflammation and immune depression contribute to SCI-associated complications is still an open question
Summary
Spinal cord injury (SCI) causes disastrous damage to patients. While intraspinal infections, ischemia, and tumors can give rise to non-traumatic SCI, the majority of SCI is caused by physical trauma to the spine from sports injuries, car accidents, falls, and gunshots. The inflammatory microenvironment following SCI is mediated by activated microglia and astrocytes, and infiltrating macrophages greatly contribute to the progression of secondary injury [2,3,4,5,6]. While much consideration should be given to the brainstem’s role in multiple organ dysfunction following SCI, this review focuses on the contributive roles of inflammation and immunity in these systemic complications.
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