Low-pressure micro-mechanical re-adaptation device sustainably and effectively improves locomotor recovery from complete spinal cord injury

Veronica Estrada,Julia Krebbers,Klaus Seide,Christian Jürgens,Hans Werner Müller,Jörg Müller,Heinrich Blazyca,Jennifer Illgen,Nicole Brazda,Rudolf Martini,Christian Voss,Hoc Khiem Trieu

doi:10.1038/s42003-018-0210-8

Abstract

Traumatic spinal cord injuries result in impairment or even complete loss of motor, sensory and autonomic functions. Recovery after complete spinal cord injury is very limited even in animal models receiving elaborate combinatorial treatments. Recently, we described an implantable microsystem (microconnector) for low-pressure re-adaption of severed spinal stumps in rat. Here we investigate the long-term structural and functional outcome following microconnector implantation after complete spinal cord transection. Re-adaptation of spinal stumps supports formation of a tissue bridge, glial and vascular cell invasion, motor axon regeneration and myelination, resulting in partial recovery of motor-evoked potentials and a thus far unmet improvement of locomotor behaviour. The recovery lasts for at least 5 months. Despite a late partial decline, motor recovery remains significantly superior to controls. Our findings demonstrate that microsystem technology can foster long-lasting functional improvement after complete spinal injury, providing a new and effective tool for combinatorial therapies.

Highlights

Traumatic spinal cord injuries result in impairment or even complete loss of motor, sensory and autonomic functions
Reactive (glial fibrillary acidic protein (GFAP)+) astrocytes were frequently detected in the mMS bridge and lumen regions (Figs. 1d and 4a)
The finding of von Willebrand factor+ endothelial cells revealed the presence of newly formed blood vessels in the lumen of the implanted mMS and showed frequent association of regenerating axon profiles with areas enriched in blood vessels (Fig. 1g)

Summary

Introduction

Traumatic spinal cord injuries result in impairment or even complete loss of motor, sensory and autonomic functions. Re-adaptation of spinal stumps supports formation of a tissue bridge, glial and vascular cell invasion, motor axon regeneration and myelination, resulting in partial recovery of motor-evoked potentials and a far unmet improvement of locomotor behaviour. The lesion scar, inflammatory reactions and the release of inhibitors can be modulated on a molecular basis, and such possibilities have led to the development of numerous therapeutic approaches to treat SCI5,9,11–28 These approaches present only limited possibilities to stabilise and re-adapt injured spinal tissue in submillimetre range. After acute severe damage of rat spinal cord by a complete transection at thoracic level T9, mMS implantation results in a significant increase in axonal regeneration across the lesion site, invasion of glial cells and myelination of regenerating axons as well as neovascularisation throughout the implant. For future preclinical and clinical applications of the mMS device, less severe lesion models will be included

Methods

Results

Conclusion