Biomarkers in Spinal Cord Injury: Prognostic Insights and Future Potentials

Abstract

Spinal Cord Injury (SCI) is a major challenge in Neurotrauma research. Complex pathophysiological processes take place immediately after the injury and later on as the chronic injury develops. Moreover, SCI is usually accompanied by traumatic injuries because the most common modality of injury is road traffic accidents and falls. Patients develop significant permanent neurological deficits that depend on the extent and the location of the injury itself and in time they develop further neurological and body changes that may risk their mere survival. In our review, we explored the recent updates with regards to SCI biomarkers. We observed two methods that may lead to the appearance of biomarkers for SCI. First, during the first few weeks following the injury the Blood Spinal Cord Barrier (BSCB) disruption that releases several neurologic structure components from the injured tissue. These components find their way to Cerebrospinal Fluid (CSF) and the systemic circulation. Also, as the injury develops several components of the pathological process are expressed or released such as in neuroinflammation, apoptosis, reactive oxygen species, and excitotoxicity sequences. Therefore, there is a growing interest in examining any correlations between these components and the degrees or the outcomes of the injury. Additionally, some of the candidate biomarkers are theorized to track the progressive changes of SCI which offers an insight on the patients' prognoses, potential-treatments-outcomes assessment, and monitoring the progression of the complications of chronic SCI such as Pressure Ulcers and urinary dysfunction. An extensive literature review was performed covering literature, published in English, until February 2018 using the Medline/PubMed database. Experimental and human studies were included and titles, PMID, publication year, authors, biomarkers studies, the method of validation, relationship to SCI pathophysiology, and concluded correlation were reported. Potential SCI biomarkers need further validation using clinical studies. The selection of the appropriate biomarker group should be made based on the stage of the injuries, the accompanying trauma and with regards to any surgical, or medical interference that might have been done. Additionally, we suggest testing multiple biomarkers related to the several pathological changes coinciding to offer a more precise prediction of the outcome.

Circulating PAMM, a novel antioxidant and anti-inflammatory protein, is elevated in acute SCI

“…Several other putative inflammatory biomarkers of SCI include interleukins, TGF-B1, insulin-like growth factor 1 (IGF-1) and soluble CD95 ligand (sCD95L). But, there are conflicting reports in the literature about the utility of each as a predictor of inflammatory-related pathologies in SCI (see for a review, [5]). To ensure accuracy and repeatability, these markers have been suggested to be used in parallel with other diagnostic biomarkers for SCI [5].…”

“…But, there are conflicting reports in the literature about the utility of each as a predictor of inflammatory-related pathologies in SCI (see for a review, [5]). To ensure accuracy and repeatability, these markers have been suggested to be used in parallel with other diagnostic biomarkers for SCI [5]. Additional work is needed to validate these candidate biomarkers prior to implementing use in clinical care.…”

“…Trauma results in primary injury due to mechanical forces leading to compression or contusion of the cord. Subsequently, secondary injury occurs via multiple mechanisms including reactive oxygen/nitrogen species (ROS/RNS) generation, glutamate-mediated excitotoxicity, cellular necrosis and apoptosis [3][4][5], and the development of neuroinflammation. Oxidative stress occurs in primary injury due to cellular releases of cytoplasmic components and mitochondrial dysfunction and persists through the secondary injury phase due to severe neuroinflammation [5].…”

“…Subsequently, secondary injury occurs via multiple mechanisms including reactive oxygen/nitrogen species (ROS/RNS) generation, glutamate-mediated excitotoxicity, cellular necrosis and apoptosis [3][4][5], and the development of neuroinflammation. Oxidative stress occurs in primary injury due to cellular releases of cytoplasmic components and mitochondrial dysfunction and persists through the secondary injury phase due to severe neuroinflammation [5]. We recently identified a novel secreted protein with both antioxidant and redox-regulating activity which we called Peroxiredoxin-like 2 activated in M-CSF stimulated monocytes (PAMM) [6,7], also known as adiporedoxin (Adrx) [8].…”

Cerebrospinal fluid levels of GFAP and pNF-H are elevated in patients with chronic spinal cord injury and neurological deterioration

“…Blood-based markers indicative of glial and neuronal injury have attracted attention over the past decades [ 37 , 39 ]. Although previous biomarker studies following acute SCI exist [ 10 , 29 , 30 , 56 ], data are lacking on spinal cord tethering [ 2 ]. Easily accessible, objective, and inexpensive biochemical markers reflecting glial scar formation and progressive neuronal damage are needed and might help to improve diagnosis, monitor ongoing pathophysiological mechanisms, and predict outcome of post-traumatic myelopathy.…”