Time-dependent changes of protein biomarker levels in the cerebrospinal fluid after blast traumatic brain injury

Time-dependent changes of protein biomarkers in the cerebrospinal fluid (CSF) can be used to identify the pathological processes in traumatic brain injury (TBI) as well as to follow the progression of the disease. We obtained CSF from a large animal model (swine) of blast-induced traumatic brain injury prior to and at 6, 24, 72 h, and 2 wk after a single exposure to blast overpressure, and determined changes in the CSF levels of neurofilament-heavy chain, neuron-specific enolase, brain-specific creatine kinase, glial fibrillary acidic protein, calcium-binding protein beta (S100 beta), Claudin-5, vascular endothelial growth factor, and von Willebrand factor using reverse phase protein microarray. We detected biphasic temporal patterns in the CSF concentrations of all tested protein markers except S100 beta. The CSF levels of all markers were significantly increased 6 h after the injury compared to preinjury levels. Values were then decreased at 24 h, prior to a second increase in all markers but S100 beta at 72 h. At 2 wk postinjury, the CSF concentrations of all biomarkers were decreased once again; brain-specific creatine kinase, Claudin-5, von Willebrand factor, and S100 beta levels were no longer significantly higher than their preinjury values while neurofilament-heavy chain, neuron-specific enolase, vascular endothelial growth factor, and glial fibrillary acidic protein levels remained significantly elevated compared to baseline. Our findings implicate neuronal and glial cell damage, compromised vascular permeability, and inflammation in blast-induced traumatic brain injury, as well as demonstrate the value of determining the temporal pattern of biomarker changes that may be of diagnostic value.