There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would be facilitated by the availability of biomarkers with which to stratify injury severity and predict neurological recovery. Cerebrospinal fluid (CSF) samples were obtained over a period of 72 h in 27 patients with complete SCI (ASIA A) or incomplete SCI (ASIA B or C). Cytokines were measured in CSF and serum samples using a multiplex cytokine array system and standard enzyme-linked immunosorbent assay (ELISA) techniques. Neurological recovery was monitored, and patient-reported neuropathic pain was documented. IL-6, IL-8, MCP-1, tau, S100beta, and glial fibrillary acidic protein (GFAP) were elevated in a severity-dependent fashion. A biochemical model was established using S100beta, GFAP, and IL-8 to predict injury severity (ASIA A, B, or C). Using these protein concentrations at 24-h post injury, the model accurately predicted the observed ASIA grade in 89% of patients. Furthermore, segmental motor recovery at 6 months post injury was better predicted by these CSF proteins than with the patients' baseline ASIA grade. The pattern of expression over the first 3 to 4 days post injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1 provides invaluable information about the pathophysiology of human SCI. A prediction model that could use such biological data to stratify injury severity and predict neurological outcome may be extremely useful for facilitating the clinical validation of novel treatments in acute human SCI.

Many therapies that have been developed for acute spinal cord injury (SCI) either influence or are influenced by posttraumatic inflammation. Many such therapies have reportedly produced promising neurologic benefits in animal models of SCI, but demonstrating convincing efficacy in human clinical trials has remained elusive. This discrepancy may be related in part to differences in the inflammatory response to SCI between human patients and the widely studied rodent models. Our objectives were, therefore, to establish the time course of inflammatory cytokine release in the spinal cord of rats after a thoracic contusion, to determine whether the cytokine release was injury dependent, and to correlate these findings with those that we have recently reported for the cerebrospinal fluid (CSF) of human SCI patients. After rodent SCI, GRO (the rat equivalent of IL-8), IL-6, IL-1α, IL-1β, IL-13, MCP-1, MIP1α, RANTES, and TNFα were elevated within the spinal cord, whereas IL-12p70 was decreased. In human SCI, IL-6, IL-8, and MCP-1 were also elevated within the cerebrospinal fluid but at later times than those observed in the rodent spinal cord. IL-6, IL-8, and MCP-1 were released in an injury-dependent manner in both the rodent model of SCI and the human condition. In this regard, similar patterns of expression were observed for a number of inflammatory cytokines after SCI in rodent spinal cords and in human CSF. Such proteins may therefore have potential utility as biomarkers and surrogate outcome measures for evaluating biological response to therapeutic interventions.

Spinal cord injuries (SCI) can result in devastating paralysis, for which there is currently no robustly efficacious neuroprotective/neuroregenerative treatment. When the spinal cord is subjected to a traumatic injury, the local vasculature is disrupted and the blood–spinal cord barrier is compromised. Subsequent inflammation and ischemia may then contribute to further secondary damage, exacerbating neurological deficits. Therefore, understanding the vascular response to SCI and the molecular elements that regulate angiogenesis has considerable relevance from a therapeutic standpoint. In this paper, we review the nature of vascular damage after traumatic SCI and what is known about the role that angiogenic proteins—angiopoietin 1 (Ang1), angiopoietin 2 (Ang2) and angiogenin—may play in the subsequent response. To this, we add recent work that we have conducted in measuring these proteins in the cerebrospinal fluid (CSF) and serum after acute SCI in human patients. Intrathecal catheters were installed in 15 acute SCI patients within 48 h of injury. CSF and serum samples were collected over the following 3–5 days and analysed for Ang1, Ang2 and angiogenin protein levels using a standard ELISA technique. This represents the first description of the endogenous expression of these proteins in an acute human SCI setting.