J Neurotrauma. 2019 Jun 19.

Possible strategies to optimize a biomarker discovery approach to correlate with neurological outcome in patients with spinal cord injury: a pilot study.

Fernandez Canales MLM1, Baldassarro VA2,3, Capirossi R4, Montevecchi R5, Bonavita J6, Cescatti M7, Giovannini T8, Giovannini G9, Uneddu M10, Gordini G11, Giardino L12,13,14, Calz? L15,16,17.
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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, also impairing appropriate rehabilitation care. The sparse available data on biochemical composition of the cerebrospinal fluid (CSF) during acute and/or chronic phase of the lesion provided up-to-now inconsistent results. In this pilot study, we then explored the possibility to combine a multiparametric and bioinformatics analysis of the CSF to its biological properties tested on different cells types, suitable to investigate inflammation and remyelination. The patients enrollment was based on stringent inclusion criteria, i.e. cervical and thoracic SCI trauma, CSF collection within 24 hours from trauma, type of surgical approach for spine stabilization, no 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 at 24h after SCI. A bioinformatic analysis indicated that 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 stimulate 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 a combined bioanalytic and biological approach to analyze SCI CSF at different times after injury could be a useful approach to identify reliable diagnostic and prognostic markers in SCI.

KEYWORDS:
BIOMARKERS; CEREBROSPINAL FLUID; GROWTH FACTORS; INFLAMMATION; TRAUMATIC SPINAL CORD INJURY

https://www.ncbi.nlm.nih.gov/pubmed/31215324