A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

Abstract

An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation.

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

“…[1][2][3] Effective treatments should ideally act on part or all of those events to finally spare tissue and preserve axonal tracts, oligodendrocytes, and myelin sheaths. No gold standard therapy for SCI has been established, [4][5][6] although clinical trials with methylprednisolone (NAS-CIS II and III) have demonstrated modest therapeutic benefits. 7,8 Progesterone (PROG) could represent a good candidate for therapy, because it is neuroprotective, promyelinating, and antiinflammatory in pathologies of peripheral and central nervous systems.…”

Phosphorylated neurofilament subunit NF-H as a biomarker for evaluating the severity of spinal cord injury patients, a pilot study

“…3 Therefore, many pharmacological and tissue-engineering therapies are now designed to be applied within the first month after injury. 4,5 One of the obstacles against the innovation of novel therapies for SCI is the difficulty of determining the baseline severity of the injury. During the early period after injury when novel therapies would be applied, unstable conditions of patients, including the phenomenon of spinal shock, prevent precise evaluation of neurological status.…”

Spinal cord injury and its treatment: current management and experimental perspectives

“…Some degree of preservation of the connections between the supraspinal centres and the sub-lesional cord would lead to lessened neurological deficits. However, although neuroprotective strategies were designed for potentially rapid clinical application and have been intensively investigated (see below), the ''magic bullet'' has yet to be found (for detailed recent reviews, see [55,56]). …”