Elevated serum and cerebrospinal fluid levels of the synaptophysin and neurogranin with its altered brain expression in the early phase of traumatic brain injury as a potential marker of synaptic injury.

Abstract

Traumatic brain injury (TBI) is a significant contributor to mortality and is frequently linked to forensic and criminological inquiries. In the context of scientific and clinical progress, there is a continual need to explore new bioassays and data analysis methods for use in TBI diagnostics in both ante- and post-mortem individuals. Predominantly intra- and extra-synaptic proteins, such as synaptophysin (SYP) and neurogranin (NRGN) were to date potentially investigated as markers for TBI regarding their usefulness as a set of reliable biomarkers. This study aimed to elucidate and identify if elevated SYP and NRGN concentration levels in biofluids such as serum and CSF are seen in cases of TBI in a population-based autopsy screening. An additional comparative examination of the SYP and NRGN protein expression in the obtained brain tissue by performing immunohistochemical staining was done. The study was carried out using cases (n = 20) of severe head injury suspected as the cause of death and control cases (n = 20) of sudden death in the mechanism of cardiopulmonary failure. The biofluids, such as serum and cerebrospinal fluid (CSF) were collected within ∼24 h after death and compared using ELISA test. Brain specimens were similarly collected during forensic autopsies. In our study, we observed the elevated concentration levels of SYP and NRGN in serum and CSF. In anti-SYP staining of the frontal cortex, a significant, generalized reduction in the reaction was observed, within neurons and neuropil in the head injury group. In anti-NRGN staining of the frontal cortex, a significant, generalized homogenization of the reaction was observed both within the neuronal bodies and their axons. The possible implementation of synaptic biomarker assays offers an interesting and novel tool for investigation and research regarding TBI diagnosis and pathogenesis. This surrogate synatpic assay could be useful in clinical prognosis and risk calculation of non-fatal cases of TBI, regarding the development of neurodegenerative conditions of TBI individuals.