Traumatic brain injury (TBI) is a heterogeneous disease, and the discovery of diagnostic and prognostic TBI
biomarkers is highly desirable in order to individualize patient care. We have previously published a study in which we identified possible TBI
biomarkers by mass spectrometry 24 h after injury in a cell culture model.
Ezrin-
radixin-
moesin (ERM)
proteins were found abundantly in the medium after
trauma, and in the present study we have identified extracellular
ezrin as a possible
biomarker for
brain trauma by analyzing cell culture medium from injured primary neurons and glia and by measuring
ezrin in cerebrospinal fluid (CSF) from both rats and humans. Our results show that extracellular
ezrin concentration was substantially increased in cell culture medium after injury, but that the intracellular expression of the
protein remained stable over time. Controlled cortical impact injured rats showed an increased amount of
ezrin in CSF at both day 3 and day 7 after
trauma. Moreover,
ezrin was present in all ventricular CSF samples from seven humans with severe TBI. In contrast to intracellular
ezrin, which is distinctly activated following TBI, extracellular
ezrin is nonphosphorylated. This is the first report of extracellular ERM
proteins in human and experimental models of TBI, providing a scientific foundation for further assessment of
ezrin as a potential
biomarker.