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Serum concentrations of the axonal injury marker neurofilament light protein are not influenced by blood-brain barrier permeability

Journal article
Authors Marie Kalm
Martina Boström
Åsa P Sandelius
Yohanna Eriksson
C. Joakim Ek
Kaj Blennow
Thomas Bjork-Eriksson
Henrik Zetterberg
Published in Brain Research
Volume 1668
Pages 12-19
ISSN 0006-8993
Publication year 2017
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Clinical Sciences, Section for Oncology, Radiation Physics, Radiology and Urology, Department of Oncology
Pages 12-19
Language English
Links doi.org/10.1016/j.brainres.2017.05....
Keywords Biomarker, Late effects, Cranial radiotherapy, Neurotoxicity, Juvenile brain, children, tumors, chain, irradiation, inflammation, progression, biomarkers, childhood, integrity, mice, Neurosciences & Neurology, wler jf, 1989, british journal of radiology, v62, p679
Subject categories Cancer and Oncology

Abstract

A blood biomarker to monitor individual susceptibility to neuronal injury from cranial radiotherapy could potentially help to individualize radiation treatment and thereby reduce the incidence and severity of late effects. An important feature of such a blood biomarker is that its concentration is not confounded by varying degrees of release from the brain into the blood across the blood-brain barrier (BBB). In this study, we investigated serum neurofilament light protein (NFL) concentrations in 21-day old mice following a single dose of cranial irradiation (8 Gy). Cranial irradiation resulted in acute cell injury measured as a 12.9-fold increase in caspase activity 6 h after irradiation; activation of inflammation measured by levels of CCL2 and increased BBB permeability measured by C-14-sucrose concentration ratios in brain and cerebrospinal fluid (CSF). Serum levels of NFL peaked at 6 h after both anesthesia and cranial irradiation, but no timely correlation of serum NFL concentration with BBB permeability was found. Further, three groups of patients with different degrees of BBB impairment (measured as the CSF/serum albumin ratio) were investigated. There was no correlation between serum NFL concentration and CSF/serum albumin ratio (r = 0.139, p = 0.3513), however a strong correlation was found for NFL concentration in serum and NFL concentration in CSF (r = 0.6303, p < 0.0001). In conclusion, serum NFL appears to be a reliable blood biomarker for neuronal injury, and its concentration is not confounded by BBB permeability. (C) 2017 Elsevier B.V. All rights reserved.

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