Experimental Treatments for Spinal Cord Injury: A Systematic Review and Meta-Analysis

Abstract

Spinal cord injury (SCI) is characterized by a complex and prolonged injury process that exacerbates the damage induced by the primary injury and inhibits the potential for regeneration. SCI frequently results in the devastating loss of neurological functions and thus has serious consequences on patient quality of life. Current treatments are limited and focus on early interventions for the acute management of complications. Therefore, the development of novel treatments targeting ongoing injury processes is required to improve SCI outcomes. We aimed to systematically review studies published in the last 10 years that examined experimental treatments with neuroregenerative and neuroprotective capabilities for the improvement of SCI. We analyzed treatments from 44 studies that were identified through a systematic literature search using three databases: PubMed, Web of Science and EMBASE (searched through Ovid). We performed a meta-analysis for Basso-Beattie-Bresnahan (BBB) locomotion test data and collected immunohistochemistry results to demonstrate neuroregenerative and neuroprotective properties of the treatments, respectively. The two treatments that illustrated the most significant improvements in functional recovery using the BBB test were the combined use of tetrahedral framework nucleic acid (tFNA) with neural stem cells (NSCs) and Fortasyn^® Connect (FC) supplementation. Both treatments also attenuated secondary injury processes as demonstrated through immunohistochemistry. Combined tFNA with NSCs and FC supplementation are promising treatments for the improvement of SCI as they both demonstrate neuroregenerative and neuroprotective properties. Further pre-clinical testing is required to validate and determine the long-term efficacies of these treatments for the improvement of SCI.

Keywords: experimental treatments; locomotor recovery; neuroprotection; neuroregeneration; spinal cord injury.

Figure 1

PRISMA flow chart illustrating the literature search process and screening of papers included in this systematic review.

Figure 2

Meta-analysis for the effect of single treatments on the improvement of BBB scores analyzed at 28 days after spinal cord injury in nine studies [11,13,25,27,30,31,33,34,54].

Figure 3

A meta-analysis for the effect of single treatments on the improvement of BBB scores analyzed at 35 days after spinal cord injury in three studies [17,28,41].

Figure 4

A meta-analysis for the effect of single treatments on the improvement of BBB scores analyzed at 42 days after spinal cord injury in six studies [19,32,46,48,51,53].

Figure 5

A meta-analysis for the effect of single treatments on the improvement of BBB scores analyzed at 56 days after spinal cord injury in seven studies [15,18,26,29,40,47,50].

Figure 6

A meta-analysis for the effect of combined treatments on the improvement of BBB scores analyzed at the final recorded timepoints after spinal cord injury in nine studies [15,17,22,26,27,28,40,47,50].

Figure 7

A meta-analysis for the effect of all treatments on the improvement of BBB scores analysed at the final recorded timepoints after spinal cord injury in all 32 studies that performed the BBB test [11,12,13,14,15,16,17,18,19,22,25,26,27,28,29,30,31,32,33,34,37,40,41,42,43,45,46,47,48,50,51,53,54].

Figure 8

A summary diagram of the risk of bias for all 44 studies included in this review. All studies were assessed against ten different risk parameters as listed on the y-axis.

Figure 9

Diagram to represent the risk of bias in individual studies for all 44 studies included in this review [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54].