Possible Strategies to Optimize a Biomarker Discovery Approach to Correlate with Neurological Outcome in Patients with Spinal Cord Injury: A Pilot Study.

Abstract

The lack of reliable diagnostic and prognostic markers for spinal cord injured (SCI) patients is a severe obstacle in development and testing of new therapies, and it also impairs appropriate rehabilitation care. The sparse available data on the biochemical composition of cerebrospinal fluid (CSF) during the acute and/or chronic phase of the lesion provide, up until now, inconsistent results. In this pilot study, we then explored the possibility of combining a multi-parametric and bioinformatic analysis of CSF for its biological properties tested on different cells types, suitable for investigating inflammation and re-myelination. The patient enrollment was based on stringent inclusion criteria; that is, cervical and thoracic SCI trauma, CSF collection within 24 h of trauma, type of surgical approach for spine stabilization, and absence of steroid therapy before CSF collection. Eleven SCI patients and four healthy controls were included, and in three patients, CSF was also collected at 3 months after lesion. We identified 19 proteins among the 60 investigated cytokines, chemokines, growth factors, and structural biomarkers, which are transiently regulated 24 h after SCI. A bioinformatic analysis indicated that interleukin (IL)-6 and IL-10 are in the core of the interconnected net of activated proteins. Cell-based experiments indicate that CSF from SCI patients stimulates astroglia derivation from neural precursor cells, and an inverse correlation between IL-8 CSF level and oligodendrocyte precursor cells generated from neural stem cells was also observed. Results from this pilot study suggest that using a combined bioanalytic and biological approach to analyze SCI CSF at different times after injury could be a useful approach for identifying reliable diagnostic and prognostic markers in SCI.