title: The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury.
abstract: During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the "immune privileged/specialized" milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of "SCI disease" and are important therapeutic targets to improve neural repair and neurological outcome. Generic immune suppressive therapies have been largely unsuccessful, mostly because inflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, "compartimentalized" investigations, limited to only intraspinal inflammation and associated cellular or molecular changes in the spinal cord, neglect the reality that the structure and function of the CNS are influenced by systemic immune challenges and that the immune system is 'hardwired' into the nervous system. Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the context of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and "neurogenic" spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired "host-defense" and trauma-induced autoimmunity.
authors.affiliation: Department of Neurology and Experimental Neurology, Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charite - Universitatsmedizin Berlin, D-10117 Berlin, Germany.|Spinal Cord Injury Center, Trauma Hospital Berlin, D-12683 Berlin, Germany.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Schwab
authors.affiliation: Center for Brain and Spinal Cord Repair, Department of Neuroscience, Wexner Medical Center, The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Experimental Neurology, Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charite - Universitatsmedizin Berlin, D-10117 Berlin, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Kopp
authors.affiliation: Department of Neurology and Experimental Neurology, Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charite - Universitatsmedizin Berlin, D-10117 Berlin, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brommer
authors.affiliation: Center for Brain and Spinal Cord Repair, Department of Neuroscience, Wexner Medical Center, The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000502:physiology*; D002908:Chronic Disease; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D018836:Inflammation Mediators
keywords: Adaptive immune response; Autoimmunity; Innate immune response; Spinal cord injury