{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T04:35:05Z","timestamp":1766378105523,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Commission of the Heinrich-Heine-University Duesseldorf, Germany","award":["30\/2013"],"award-info":[{"award-number":["30\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal strokes may be associated with tremendous spinal cord injury. Erythropoietin (EPO) improves the neurological outcome of animals after spinal cord ischemia (SCI) and its effects on ischemia-induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are considered possible molecular mechanisms. Furthermore, sphingosin-1-phosphate (S1P) is suggested to correlate with SCI. In this study, the effect of recombinant human EPO (rhEPO) and carbamylated EPO (cEPO-Fc) on the outcome of mice after SCI and a prognostic value of S1P were investigated. SCI was induced in 12-month-old male mice by thoracic aortal cross-clamping after administration of rhEPO, cEPO-Fc, or a control. The locomotory behavior of mice was evaluated by the Basso mouse scale and S1P serum levels were measured by liquid chromatography-tandem mass spectrometry. The spinal cord was examined histologically and the expressions of key UPR proteins (ATF6, PERK, and IRE1a, caspase-12) were analyzed utilizing immunohistochemistry and real-time quantitative polymerase chain reaction. RhEPO and cEPO-Fc significantly improved outcomes after SCI. The expression of caspase-12 significantly increased in the control group within the first 24 h of reperfusion. Animals with better locomotory behavior had significantly higher serum levels of S1P. Our data indicate that rhEPO and cEPO-Fc have protective effects on the clinical outcome and neuronal tissue of mice after SCI and that the ER is involved in the molecular mechanisms. Moreover, serum S1P may predict the severity of impairment after SCI.<\/jats:p>","DOI":"10.3390\/ijms23179558","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:22:48Z","timestamp":1661300568000},"page":"9558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spinal Stroke: Outcome Attenuation by Erythropoietin and Carbamylated Erythropoietin and Its Prediction by Sphingosine-1-Phosphate Serum Levels in Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-8537","authenticated-orcid":false,"given":"Leon-Gordian","family":"Koepke","sequence":"first","affiliation":[{"name":"Department of Trauma Surgery and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3597-6276","authenticated-orcid":false,"given":"Edzard","family":"Schwedhelm","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Ibing","sequence":"additional","affiliation":[{"name":"Clinic for Vascular and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6322-7152","authenticated-orcid":false,"given":"Alexander","family":"Oberhuber","sequence":"additional","affiliation":[{"name":"Clinic for Vascular and Endovascular Surgery, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guenter","family":"Daum","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20251 Hamburg, Germany"},{"name":"Department of Vascular Medicine, University Heart and Vascular Center Hamburg, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitta","family":"Vcelar","sequence":"additional","affiliation":[{"name":"Polymun Scientific Immunbiologische Forschung GmbH, 3400 Klosterneuburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"Schelzig","sequence":"additional","affiliation":[{"name":"Clinic for Vascular and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-8554","authenticated-orcid":false,"given":"Florian","family":"Simon","sequence":"additional","affiliation":[{"name":"Clinic for Vascular and Endovascular Surgery, University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/00000658-198607000-00005","article-title":"Cross-clamping of the thoracic aorta. 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