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s\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007639","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008723","name":"Finnish Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008087","name":"Finnish Society of Anaesthesiologists","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008087","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In-hospital mortality among resuscitated out-of-hospital cardiac arrest (OHCA) patients remains high. Identifying patients who will benefit from intensive care while avoiding prolonged, potentially unnecessary treatments is essential. Blood-based biomarkers provide a novel method for evaluating brain injury. The ability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), neuron-specific enolase (NSE) and total-tau (t-tau) to measure white and grey matter injury is unestablished in comatose OHCA survivors treated with targeted temperature management (TTM) or xenon combined with TTM. We examined correlations between the biomarkers and white and grey matter injury assessed with diffusion tensor imaging (DTI). This was a randomized, single-blind, phase 2 clinical drug trial involving two multipurpose intensive care units in Finland. It was conducted between August 2009 and March 2015. One hundred and ten comatose OHCA patients aged 24 to 76 years were randomly assigned to either inhaled xenon treatment combined with 24-h TTM (33\u00b0C) (n = 55, xenon group) or TTM alone (n = 55, control group). MRI data were available from 96 patients, with a median imaging time of 53\u2005h (interquartile range, 47\u201364\u2005h) after OHCA. Biomarker data were obtained from 105 patients. In the control group of 48 patients, after adjusting for age, sex and site, a disruption of white matter microintegrity as measured by decreased fractional anisotropy (FA) of DTI, the primary endpoint of the trial, showed a significant negative correlation with NfL at 24, 48 and 72\u2005h (\u03c1 = \u22120.28 to \u22120.37; P &amp;lt; 0.05), NSE at 48 and 72\u2005h (\u03c1 = \u22120.30 to \u22120.35; P &amp;lt; 0.05) and t-tau only at 72\u2005h (\u03c1 = \u22120.30; P &amp;lt; 0.05). In the xenon group (n = 48), these correlations were absent at all timepoints. The NfL\u2013FA partial correlations showed progressive divergence between the xenon and control groups, with a statistically significant between-group difference observed at 72\u2005h (\u03c1 = \u22120.37 versus \u03c1 = 0.14; P = 0.016). Cortical or basal ganglia grey matter mean diffusivity did not have a consistent correlation with biomarker levels at different time points. No statistically significant differences were found between the xenon and control groups in the adjusted geometric mean levels of GFAP, NfL, NSE or t-tau at various time points following OHCA. In conclusion, NfL correlated with FA in controls but not in the xenon group. This between-group difference reached significance at 72\u2005h, suggesting that xenon may modify the relationship between axonal injury and white matter microstructure after OHCA.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag378","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:51:47Z","timestamp":1791373907000},"source":"Crossref","is-referenced-by-count":0,"title":["Correlation of blood biomarkers with microstructural brain injury in survivors of out-of-hospital cardiac arrest"],"prefix":"10.1093","volume":"8","author":[{"given":"Mikael V","family":"Laaksonen","sequence":"first","affiliation":[{"name":"Department of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi P","family":"Posti","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital and University of Turku , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carita C","family":"Hollm\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Turku, Turku University Hospital , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg , S-431 80 M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , S-431 80 M\u00f6lndal ,","place":["Sweden"]},{"name":"Paris Brain Institute, ICM, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Sorbonne University , 75646 Paris Cedex 13 ,","place":["France"]},{"name":"Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC , Hefei 230026 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg , S-431 80 M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , S-431 80 M\u00f6lndal ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology , London WC1E 6BT ,","place":["UK"]},{"name":"UK Dementia Research Institute at UCL , London WC1E 6BT ,","place":["UK"]},{"name":"Hong Kong Center for Neurodegenerative Diseases , The Hong Kong University of Science and Technology, Hong Kong ,","place":["China"]},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53792-2420 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko K","family":"Rinne","sequence":"additional","affiliation":[{"name":"Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital and University of Turku , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami M","family":"Virtanen","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Turku, Turku University Hospital , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jani P","family":"Saunavaara","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Turku University Hospital and University of Turku , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riitta K","family":"Parkkola","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Turku, Turku University Hospital , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruut M","family":"Laitio","sequence":"additional","affiliation":[{"name":"Department of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli J","family":"Arola","sequence":"additional","affiliation":[{"name":"Department of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja S","family":"Hynninen","sequence":"additional","affiliation":[{"name":"Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmi K","family":"Ylikoski","sequence":"additional","affiliation":[{"name":"Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha A","family":"Martola","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Helsinki and Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjaana S","family":"Tiainen","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Helsinki and Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risto O","family":"Roine","sequence":"additional","affiliation":[{"name":"Division of Clinical Neurosciences, University of Turku, Turku University Hospital , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Scheinin","sequence":"additional","affiliation":[{"name":"Department of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku , 20521 Turku 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,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo T","family":"Laitio","sequence":"additional","affiliation":[{"name":"Department of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku , 20521 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Xe-HYPOTHECA Working 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