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The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury
Open accessAbstract
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 nflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, “compartmentalized” 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 is 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 face 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.
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“which is impaired in individuals with UMNDs such as MS, BI, stroke, and SCI.46–50”
From Feasibility, Acceptability, and Efficacy of Mindfulness Training in People With Upper Motor Neuron Disorders: A Systematic Review (2022) · cites this paper as [50]
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“Immediately after injury the spinal cord undergoes massive cellular and molecular changes, including increased cell death [64, 65], infiltration of inflammation cells in the lesion [2–6], axon degeneration [7–10], and OL and myelin loss [13–16, 66, 67].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [5]
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Metadata
- Authors
- Schwab, J. M., Zhang, Y., Kopp, M. A., Brommer, B., & Popovich, P. G.
- Affiliations
- Stiftung Charité (DE)
- The Ohio State University Wexner Medical Center (US)
- Corresponding author
- Schwab, Jan M.
- Popovich, Phillip G.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 258
- Pages
- 121-129
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC4099970
- OpenAlex
- W1991275594
- Semantic Scholar
- 4a08f8b28fb79888e283c1be793ea654af48618a
- Cited by
- 260
- References
- 117
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 17 · 2023: 24 · 2022: 35 · 2021: 32 · 2020: 30 · 2019: 22 · 2018: 17 · 2017: 22 · 2016: 17 · 2015: 9 · 2014: 4
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-11-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS047175, R21NS067260)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- chronic spinal cord injury, neuroinflammation, systemic immune suppression, autoimmunity, traumatic spinal cord injury, systemic inflammatory response syndrome, compensatory anti-inflammatory response syndrome, immune privilege, secondary injury, glial activation, neurodegeneration, host defense
- MeSH terms
- Animals, Chronic Disease, Humans, Immune Tolerance, Inflammation, Spinal Cord Injuries, Autoimmunity, Inflammation Mediators
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