Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries—A Prospective Cohort Study
Santtu Hellström,
Antti Sajanti,
Abhinav Srinath,
Carolyn Bennett,
Romuald Girard,
Ying Cao,
Janek Frantzén,
Fredrika Koskimäki,
Johannes Falter,
Seán B. Lyne,
Tomi Rantamäki,
Riikka Takala,
Jussi P. Posti,
Susanna Roine,
Jukka Puolitaival,
Miro Jänkälä,
Sulo Kolehmainen,
Melissa Rahi,
Jaakko Rinne,
Eero Castrén,
Janne Koskimäki
Affiliations
Santtu Hellström
Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, University of Turku, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland
Antti Sajanti
Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, University of Turku, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland
Abhinav Srinath
Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, 5841 S. Maryland, Chicago, IL 60637, USA
Carolyn Bennett
Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, 5841 S. Maryland, Chicago, IL 60637, USA
Romuald Girard
Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, 5841 S. Maryland, Chicago, IL 60637, USA
Ying Cao
Department of Radiation Oncology, Kansas University Medical Center, Kansas City, KS 66160, USA
Janek Frantzén
Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, University of Turku, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland
Fredrika Koskimäki
Neurocenter, Acute Stroke Unit, Turku University Hospital, P.O. Box 52, 20521 Turku, Finland
Johannes Falter
Department of Neurosurgery, University Medical Center of Regensburg, 93053 Regensburg, Germany
Seán B. Lyne
Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Tomi Rantamäki
Laboratory of Neurotherapeutics, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences and Drug Research Program, 00100 Helsinki, Finland
Riikka Takala
Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, P.O. Box 52, 20521 Turku, Finland
Jussi P. Posti
Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, University of Turku, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland
Susanna Roine
Neurocenter, Acute Stroke Unit, Turku University Hospital, P.O. Box 52, 20521 Turku, Finland
Jukka Puolitaival
Department of Neurosurgery, Oulu University Hospital, P.O. Box 25, 90029 Oulu, Finland
Miro Jänkälä
Department of Neurosurgery, Oulu University Hospital, P.O. Box 25, 90029 Oulu, Finland
Sulo Kolehmainen
Neuroscience Center, HiLIFE, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland
Melissa Rahi
Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, University of Turku, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland
Jaakko Rinne
Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, University of Turku, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland
Eero Castrén
Neuroscience Center, HiLIFE, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland
Janne Koskimäki
Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, University of Turku, P.O. Box 52, Hämeentie 11, 20521 Turku, Finland
Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients’ outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53–89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83–65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p < 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.
