The rocky road to translation in spinal cord repair

Abstract

Over the past 2 decades, the biological understanding of the mechanisms underlying structural and functional repair of the injured central nervous system has strongly increased. This has resulted in the development of multiple experimental treatment strategies with the collective aim of enhancing and surpassing the limited spontaneous recovery occurring in animal models and ultimately humans suffering from spinal cord or brain injuries. Several of these experimental treatments have revealed beneficial effects in animal models of spinal cord injury. With the exception of neurorehabilitative therapies, however, therapeutic interventions that enhance recovery are currently absent within the clinical realm of spinal cord injury. The present review surveys the prospects and challenges in experimental and clinical spinal cord repair. Major shortcomings in experimental research center on the difficulty of closely modeling human traumatic spinal cord injury in animals, the small number of investigations done on cervical spinal injury and tetraplegia, and the differences in lesion models, species, and functional outcome parameters used between laboratories. The main challenges in the clinical field of spinal cord repair are associated with the standardization and sensitivity of functional outcome measures, the definition of the inclusion/exclusion criteria for patient recruitment in trials, and the accuracy and reliability of an early diagnosis to predict subsequent neurological outcome. Research and clinical networks were recently created with the goal of optimizing animal studies and human trials. Promising clinical trials are currently in progress. The time has come to translate the biologic-mechanistic knowledge from basic science into efficacious treatments able to improve the conditions of humans suffering from spinal cord injury.

Bilateral Contusion-Compression Model of Incomplete Traumatic Cervical Spinal Cord Injury

“…21,22 Approximately 70% of all traumatic cervical injuries result in incomplete lesions. 23 Here, we present a rat model of bilateral incomplete cSCI that has neurobehavioral and -anatomical similarities to this condition in humans.…”

New Aspects of Graft-induced Central Plasticity and Neuroregeneration at T 10 in a Rat Model†

“…Until now, traumatic paraplegia by severance of the spinal cord (SC) remains an irreversible condition. Basically, current clinical treatment strategies are targeted to promote axon regeneration and outgrowth beyond the scar formation following SC avulsion [1][2][3][4][5][8][9][10][11][12][13][14][15][16][17][18][20][21][24][25][26][27][28][29][30][31][72][73][74][75][76][77][78][79][80][81][82][83][84][85] Previous experimental and clinical studies together with GB have aroused some hope that paraplegic patients might achieve some selective voluntary muscle reinnervation after grafting the first motor neuron to skeletal hip muscles [10,11,25,72,73].…”

“…Additionally, even sensory axons grow long distances in injured dorsal columns after peripheral nerve lesions [79]. On routine histology, it was impossible for us to determine the exact origins of the axons that grew near or inside the SNG.…”

The Application of Stem Cell Based Tissue Engineering in Spinal Cord Injury Repair.

“…However, with the development of novel stem cell and tissue engineering based treatment strategies, there are some promising preclinical results which raise hope for SCI treatment in the future. Endeavor should be made not only towards an appropriate structural repair but also importantly a satisfactory functional recovery [9].…”