A Systematic Review of Directly Applied Biologic Therapies 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 reviewed the available preclinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we reviewed 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 included: 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 spinal cord injury 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 preclinical 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.

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

“…The treated spinal cords also contained more 5HT+ fibers and vGluT1-positive buttons in the upper lumbar segments, suggesting improved plasticity of the propriospinal projection system that interacts actively with the 5HT+ reticulospinal fibers in the CPG region (Fig. 6G) (46)(47)(48)(49). We also observed that at T10-T11, the engrafted and still undifferentiated hMSCs [i.e., stromal cell antigen 1 (STRO-1)+ cells] significantly augmented surrounding host cells' expression of connexin 43 (Cx43), the main gap junction-forming protein unit between neural cells, NSCs and inflammatory cells (32,50), compared with controls (Fig.…”

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

“…A number of pharmacological approaches addressing these issues also are being investigated for promoting plasticity after experimental SCI (reviewed in Kwon et al [58]). In the next paragraphs, we will focus on selected pharmacological approaches that ultimately may be used to treat SCI in patients (Table 1).…”

Mesenchymal Stromal Cells and Neural Stem Cells Potential for Neural Repair in Spinal Cord Injury and Human Neurodegenerative Disorders

“…The inflammatory events, together with ischemia, Ca2+ influx into cells, edema, and progressive hemorrhagic necrosis significantly contribute to secondary injury, which causes progressive cavitation and loss of spinal tissue (Kwon et al 2010). The expression of adverse neurite growth-inhibitory molecules in the extracellular matrix (Fawcett, 2006;Schwab, 2004) together with lack of trophic factor support and the discontinuity of axonal projections caused by progressive tissue cyst formation pose multifactor obstacles contributing to the loss of spinal cord regeneration and inability to find an effective therapy (Nagahara & Tuszynski, 2011).…”