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.

The effect of early mobilisation (< 14 days) on pathophysiological and functional outcomes in animals with induced spinal cord injury: a systematic review with meta-analysis

“…Severity and level of spinal injury influence patterns of recovery [ 58 ]. Most studies reported on thoracic injury induced by contusion, although outcomes from cervical injuries and transections were also included, with severity not easily ascertained.…”

“…Studies also lacked standardisation in measurement and reporting of BDNF, making it difficult to consolidate or compare findings across the studies. The BBB scale is regarded as a standardised and reliable functional measure for use in rats, also widely used in mice, however, clinically significant change scores are yet to be determined, nor a clear understanding of how this translates to functional change in humans [ 23 , 58 ].…”

Hypothermia effects on neuronal plasticity post spinal cord injury

“…Most therapeutic interventions are designed to either stop or slow the progress of injury or are palliative to relieve symptoms. Unfortunately, therapeutic options are even less effective in patients suffering from the chronic form of SCI [10,11].…”

Electrical stimulation for the treatment of spinal cord injuries: A review of the cellular and molecular mechanisms that drive functional improvements

“…Current clinical management of SCI involves immediate stabilization of the vertebral column and early spinal cord decompression, followed by extensive physical rehabilitation (Fehlings et al, 2017). Beyond this, treatment options that promote significant neurological and functional recovery remain limited (Khan and Ahmed, 2022). Extensive research efforts have Dorrian et al 10.3389/fncel.2023.1095259 developed several novel interventions currently under investigation.…”

“…Electrical stimulation has a long history of therapeutic use, despite a paucity of mechanistic understanding. Electrical stimulation was first used in ancient Rome, where shocks from torpedo ray fish were used for treating headaches and gout (Kellaway, 1946;Khan and Ahmed, 2022). However, there was little understanding of the role of electricity in the nervous system until the late 1700s, when Luigi Galvani, aided by his wife Lucia, successfully conducted electricity through a frog's nerves (Galvani, 1791).…”