Dynamics of biomarkers across the stages of traumatic spinal cord injury - implications for neural plasticity and repair

Background: Traumatic spinal cord injury (SCI) is a complex medical condition causing significant physical disability and psychological distress. While the adult spinal cord is characterized by poor regenerative potential, some recovery of neurological function is still possible through activation of neural plasticity mechanisms. We still have limited knowledge about the activation of these mechanisms in the different stages after human SCI. Objective: In this review, we discuss the potential role of biomarkers of SCI as indicators of the plasticity mechanisms at work during the different phases of SCI. Methods: An extensive review of literature related to SCI pathophysiology, neural plasticity and humoral biomarkers was conducted by consulting the PubMed database. Research and review articles from SCI animal models and SCI clinical trials published in English until January 2021 were reviewed. The selection of candidates for humoral biomarkers of plasticity after SCI was based on the following criteria: 1) strong evidence supporting involvement in neural plasticity (mandatory); 2) evidence supporting altered expression after SCI (optional). Results: Based on selected findings, we identified two main groups of potential humoral biomarkers of neural plasticity after SCI: 1) neurotrophic factors including: Brain derived neurotrophic factor (BDNF), Nerve growth factor (NGF), Neurotrofin-3 (NT-3), and Insulin-like growth factor 1 (IGF-1); 2) other factors including: Tumor necrosis factor-alpha (TNF-alpha), Matrix Metalloproteinases (MMPs), and MicroRNAs (miRNAs). Plasticity changes associated with these biomarkers often can be both adaptive (promoting functional improvement) and maladaptive. This dual role seems to be influenced by their concentrations and time-window during SCI. Conclusions: Further studies of dynamics of biomarkers across the stages of SCI are necessary to elucidate the way in which they reflect the remodeling of neural pathways. A better knowledge about the mechanisms underlying plasticity could guide the selection of more appropriate therapeutic strategies to enhance positive spinal network reorganization.