Introduction
Spinal cord injury (SCI) represents a global medical and social problem that causes death and disability, the incidence of which varies from ∼15–54 cases per 1,000,000.1–3 In spite of the impressive advancement in medical and surgical treatments and the large body of pre-clinical evidence on the cellular and molecular mechanisms leading to the spinal cord damage following trauma, SCI is considered a incurable condition. In fact, currently, pharmacological interventions are still limited and are aimed at reducing edema, and the routine use of steroids has been largely abandoned and considered a “harmful standard of care.”4 Some drugs, approved for other neurological diseases, are currently being tested (e.g., riluzole, erythropoietin, Nogo-A targeting, Rho inhibitor cethrin, and minocycline). However, to date, no studies have shown evidence of recovery of neurological function. In addition, many of the current therapeutic attempts focus on complications.5
Pre-clinical and translational studies have highlighted the molecular pathology that follows trauma, divided into three phases: acute (a few seconds or minutes after the injury), secondary (from a few minutes to a few weeks after the injury), and chronic (some months to years after the injury).6 In the acute phase, mechanic and vascular events are prevalent, such as edema and alterations of the chemical microenvironment, where excitotoxicity and infiltration by circulating macrophages prevails. Many of these events are also present in the secondary phase, in particular oxidative stress, inflammation, and immunological reaction also mediated by microglial cells, which lead to the initiation of astroglial scarring, extensive demyelination, and electrophysiological collapse. In the chronic phase, demyelination, astroglial reaction, and central cavitation continue and are prevalent. Regeneration attempts; for example, axonal sprouting by some neurons, actually exacerbates alterations in the anatomy and physiology of microcircuits, such as hematoma, ischemia, necrosis, and peri-hemorrhagic edema. Re-myelination attempts are also present in this context, but many axons remain demyelinated,7 probably because oligodendrocyte precursor cells (OPCs), the re-myelinating cells in the central nervous system (CNS), fail to mature into myelinating oligodendrocytes because of severe tissue inflammation.8,9
Therefore, biochemical analysis of cerebrospinal fluid (CSF) composition at specific times after the trauma has been pursued for lesion severity and prognostic biomarker discovery. However, results from these studies are poor and contrasting.10,11
