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Dysregulated or non-resolving inflammatory processes can disturb neuronal homeostasis and drive neurodegeneration. Here, we provide an in-depth characterization of innate and adaptive inflammatory responses as well as oxidative tissue injury in human traumatic spinal cord injury lesions compared to non-traumatic control cords. In the lesion core, microglia were rapidly lost while intermediate (co-expressing pro- as well as anti-inflammatory molecules) blood-borne macrophages dominated. In contrast, in the surrounding rim, TMEM119+ microglia numbers were maintained through local proliferation and demonstrated a predominantly pro-inflammatory phenotype. Lymphocyte numbers were low and mainly consisted of CD8+ T cells. Only in a subpopulation of patients, CD138+\/IgG+ plasma cells were detected, which could serve as candidate cellular sources for a developing humoral immunity. Oxidative neuronal cell body and axonal injury was visualized by intracellular accumulation of amyloid precursor protein (APP) and oxidized phospholipids (e06) and occurred early within the lesion core and declined over time. In contrast, within the surrounding rim, pronounced APP+\/e06+ axon-dendritic injury of neurons was detected, which remained significantly elevated up to months\/years, thus providing mechanistic evidence for ongoing neuronal damage long after initial trauma. Dynamic and sustained neurotoxicity after human spinal cord injury might be a substantial contributor to (i) an impaired response to rehabilitation; (ii) overall failure of recovery; or (iii) late loss of recovered function (neuro-worsening\/degeneration).<\/jats:p>","DOI":"10.1093\/brain\/awaa360","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T23:30:28Z","timestamp":1601940628000},"page":"144-161","source":"Crossref","is-referenced-by-count":200,"title":["Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-1591","authenticated-orcid":false,"given":"Tobias","family":"Zrzavy","sequence":"first","affiliation":[{"name":"Department of Neurology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Schwaiger","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Wimmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Bauer","sequence":"additional","affiliation":[{"name":"Center for Brain Research, Medical University of Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Butovsky","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Wome\u0144s Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M","family":"Schwab","sequence":"additional","affiliation":[{"name":"The Belford Center for Spinal Cord Injury, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Neurology, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Physical Medicine & Rehabilitation, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Lassmann","sequence":"additional","affiliation":[{"name":"Center for Brain Research, Medical University of Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5769-1100","authenticated-orcid":false,"given":"Romana","family":"H\u00f6ftberger","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"2021021220574039800_awaa360-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2017.18","article-title":"Traumatic spinal cord injury","volume":"3","author":"Ahuja","year":"2017","journal-title":"Nat Rev Dis 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