Grey matter volume reduction and its association with brain-enriched blood biomarkers in out-of-hospital cardiac arrest survivors

Elevated levels of blood-based biomarkers such as neurofilament light chain (NfL) and neuron-specific enolase (NSE) are associated with poor neurological outcome after out-of-hospital cardiac arrest (OHCA). This study investigates the relationship between regional grey matter volume reduction and levels of glial fibrillary acidic protein (GFAP), NfL, NSE, and total-tau (t-tau) protein. This substudy of the Xe-Hypotheca trial included 110 patients randomized to receive either inhaled xenon with target temperature management (TTM) at 33 °C for 24 h (n = 55) or TTM alone (n = 55). Voxel-based morphometry was used to assess grey matter volume changes in MRI scans acquired 36-52 h and 10 days after OHCA in 45 survivors. Blood biomarkers were measured upon intensive care unit arrival and at 24, 48 and 72 h post-OHCA. NfL levels positively correlated with grey matter volume reduction in the thalamus and cingulate cortex at 24 h post-OHCA. T-tau showed more extensive pattern of significant correlations, increasing in both magnitude and spatial extent from baseline to 48 h post-OHCA. No significant biomarker-volume associations were observed for GFAP or NSE, and no treatment group differences were detected. Elevated NfL and t-tau levels were associated with region-specific grey matter volume reduction within the first 10 days after OHCA. Among the four biomarkers studied, t-tau demonstrated the strongest and most widespread associations, suggesting its potential as a marker for early ischemic grey matter volume reduction after OHCA. ClinicalTrials.gov NCT00879892, 13/04/2009.

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Journal
Scientific Reports
Published
2025-11-26
DOI
https://doi.org/10.1038/s41598-025-26322-4
Primary Topic
Cardiac Arrest and Resuscitation
Type
article
Field-Weighted Citation Impact
0.00

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article

Grey matter volume reduction and its association with brain-enriched blood biomarkers in out-of-hospital cardiac arrest survivors

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Grey matter volume reduction and its association with brain-enriched blood biomarkers in out-of-hospital cardiac arrest survivors

Eija Nukarinen, Kirsi Korpi, Riitta Parkkola, Juha Martola, Juhani K.E. Airaksinen, Victor Vorobyev, Juha Grönlund, Tero J. Vahlberg, Leena Valanne, Antti Saraste, Heli Silvennoinen, Emmi K. Ylikoski, Marjaana Tiainen, Jani P. Saunavaara, Jussi Niiranen, Marjut Varpula, Johanna E. Wennervirta, Outi Inkinen, Veli‐Pekka Harjola, Jussi P. Posti, Ruut M. Laitio, Mervyn Maze, Timo T. Laitio, Päivi Silvasti, Olli Arola, Kaj Blennow, Risto O. Roine, Mikko Pietilä, Klaus Tapio Olkkola, Carita C. Hollmén, Sami M. M. Virtanen, Minna Bäcklund, Henrik Zetterberg, Marja S. Hynninen
article en

Abstract

Elevated levels of blood-based biomarkers such as neurofilament light chain (NfL) and neuron-specific enolase (NSE) are associated with poor neurological outcome after out-of-hospital cardiac arrest (OHCA). This study investigates the relationship between regional grey matter volume reduction and levels of glial fibrillary acidic protein (GFAP), NfL, NSE, and total-tau (t-tau) protein. This substudy of the Xe-Hypotheca trial included 110 patients randomized to receive either inhaled xenon with target temperature management (TTM) at 33 °C for 24 h (n = 55) or TTM alone (n = 55). Voxel-based morphometry was used to assess grey matter volume changes in MRI scans acquired 36-52 h and 10 days after OHCA in 45 survivors. Blood biomarkers were measured upon intensive care unit arrival and at 24, 48 and 72 h post-OHCA. NfL levels positively correlated with grey matter volume reduction in the thalamus and cingulate cortex at 24 h post-OHCA. T-tau showed more extensive pattern of significant correlations, increasing in both magnitude and spatial extent from baseline to 48 h post-OHCA. No significant biomarker-volume associations were observed for GFAP or NSE, and no treatment group differences were detected. Elevated NfL and t-tau levels were associated with region-specific grey matter volume reduction within the first 10 days after OHCA. Among the four biomarkers studied, t-tau demonstrated the strongest and most widespread associations, suggesting its potential as a marker for early ischemic grey matter volume reduction after OHCA. ClinicalTrials.gov NCT00879892, 13/04/2009.

Scientific ReportsVol. 15(1)
University of Science and Technology of China (CN), University of Helsinki (FI), University of Wisconsin–Madison (US), University of Turku (FI), University of California, San Francisco (US), Hong Kong University of Science and Technology (HK), Helsinki University Hospital (FI), Sahlgrenska University Hospital (SE), Turku University Hospital (FI), Sorbonne Université (FR), Institut de Myologie (FR), Pitié-Salpêtrière Hospital (FR), UK Dementia Research Institute (GB), MRC Prion Unit (GB), University College London (GB), Indian Institute of Science Bangalore (IN), University of Gothenburg (SE)
European Commission, Vetenskapsrådet, Turun Yliopistollinen Keskussairaala, HORIZON EUROPE Framework Programme
Openalex Percentile: Top 48%
Cardiac Arrest and Resuscitation
DOIOpen Access PDFOpenAlex
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