{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:12:33Z","timestamp":1784171553319,"version":"3.55.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHA 1838\/4\u20101"],"award-info":[{"award-number":["SCHA 1838\/4\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHA 1838\/4\u20102"],"award-info":[{"award-number":["SCHA 1838\/4\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Traumatic brain injury is one of the most common cerebral incidences worldwide. Repetitive mild traumatic brain injuries occurring, for example, in athletes or victims of abuse, can cause chronic neurodegeneration due to neuroinflammation, in which the crosstalk between reactive astrocytes and activated microglia is crucial for modulating neuronal damage. The inducible enzyme heme oxygenase\u20101 and its product carbon monoxide are known to be ascribed neuroprotective and anti\u2010inflammatory properties. We caused repetitive mild traumatic brain injuries in wild\u2010type mice compared to mice without microglial heme oxygenase\u20101 expression. Additionally, mice were treated daily with either air or carbon monoxide exogenously. In wild\u2010type mice, we observed enhanced microglia activation and astrogliosis as well as vasodilation after repetitive trauma. In heme oxygenase\u20101 knockout mice, we observed enhanced activation of microglia and astrocytes at baseline pretrauma with a lack of an adequate inflammatory response to repetitive injury. However, the knockout led to enhanced NF\u2010\u03baB and IFN\u03b3 expression in the post\u2010trauma period. Carbon monoxide exerted neuroprotection, as suggested by reduced wake\u2010up times in mice and by beneficially altering inflammation post\u2010traumatic brain injury. This study further underlines the crucial role of the heme oxygenase\u20101\/carbon monoxide system in the modulation of neuronal damage and the associated neuroinflammatory response after repetitive traumatic brain injury.<\/jats:p>","DOI":"10.1111\/ejn.16666","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T02:16:40Z","timestamp":1737598600000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Severity of Repetitive Mild Traumatic Brain Injury Depends on Microglial Heme Oxygenase\u20101 and Carbon Monoxide"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1667-1311","authenticated-orcid":false,"given":"Sandra","family":"Kaiser","sequence":"first","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Fritsch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4221-3736","authenticated-orcid":false,"given":"Lena","family":"Jakob","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2120-788X","authenticated-orcid":false,"given":"Nils","family":"Schallner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c00823"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2011.10.012"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000202"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01323"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600147"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000094160"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2018.03.020"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02914"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.2217\/nmt-2016-0017"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3171\/2017.10.JNS17352"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00208"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.10.014"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005522"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22978"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153353"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-023-00371-w"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10493-6"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.02.016"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8100496"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031680"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23864"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13125"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90602"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-016-0138-3"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22581"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0355-z"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062422"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10975"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2024.2355008"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e318265a439"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/74680"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191150"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1103416"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.523480"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78443"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2014.3650"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20965786"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.11.012"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0619-8"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94773-6"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1970.tb49799.x"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8020194"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098434"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-011-9292-5"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115608"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-021-01515-5"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23523"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105704"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-42813-8"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjtee.2018.02.003"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106629"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00580"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-010-8098-4"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.647420"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23878"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.855701"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0765-z"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.11.052"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.16666","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ejn.16666","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.16666","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:33:57Z","timestamp":1777865637000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.16666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/ejn.16666"],"URL":"https:\/\/doi.org\/10.1111\/ejn.16666","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/EJN.16666\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16666\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16666\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16666\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16666\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16666\/v2\/response1","asserted-by":"object"}]},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e16666"}}