Spinal cord injury research goes from strength to strength
medwireNews: Technological advances allowing movement restoration in a man with quadriplegia, rodent studies showing successful regeneration of corticospinal projection, and improved understanding and treatment of systemic immune suppression in spinal cord injury (SCI) have been reported in three Nature publications, offering possibilities for clinical translation and hope to patients with SCI.
Electronic ‘neural bypass system’ leads to functional movement
A man with C5/C6 quadriplegia has achieved functional movement in his wrist and fingers for the first time thanks to an intracortical microelectrode implant and a neuromuscular electrical stimulation system that allows disconnected pathways in the neural system to be bypassed.
The implant records neuronal activity from the motor cortex as the participant visualises specific movements in his right hand following video cues. The data are then continuously decoded by a computer for each movement and communicated via the neuromuscular electrical stimulation system to 130 electrodes in a flexible sleeve worn on the forearm to evoke the same movement.
As reported in Nature, the patient can use the system to achieve continuous control of six different wrist and hand motions, with an overall accuracy of 70.4%. Accuracy for performing individual movements ranged from 93.1% for wrist flexion to 97.3% for thumb flexion. And his Manual Muscle Test strength improved from cervical (C) 6 to C7–C8, his gross grasping ability from C7–C8 to C8–thoracic(T)1 and his prehensile skills from C5 to C6.
The system also allowed him to complete the functional task of grasping a bottle, pouring its contents into a jar and then picking up and holding a stick to stir the contents – something he was not able to do before.
Researcher Chad Bouton (Battelle Memorial Institute, Columbus, Ohio, USA) and colleagues believe “the electronic neural bypass presented here demonstrates what is possible in the future and can offer hope for movement restoration to people living with paralysis worldwide.”
Successful corticospinal regeneration with neural progenitor cell grafts
Researchers have successfully transplanted neural progenitor cell (NPC) grafts into the severed spinal cords of rats and observed the subsequent extensive regeneration of corticospinal axons into complete spinal cord transection sites.
“Having the means in hand to extensively regenerate the corticospinal projection provides an important tool for both future clinical development and for elucidating our understanding of the mechanisms that underlie the regeneration of what has been the most refractory axonal system crucial for human motor function”, say Mark Tuszynski (University of California, San Diego, La Jolla, USA) and co-researchers.
Electrophysiological measures confirmed excitatory synaptic responses from the regenerated corticospinal axons within the graft and the rats showed improved mobility in their forelimbs.
Four findings of note emerging from the research, published in Nature Medicine, were:
- Regeneration formed complete spinal cord transection sites, rather than only growing through spared tissue bridges.
- Corticospinal axon regeneration from the graft extended beyond the lesion site into caudal host grey matter, associated with attenuation of the glial scar – a known barrier to neural repair.
- The grafts had to be derived from spinal cord rather than other parts of the nervous system, although regeneration was independent of graft maturity.
- Corticospinal regeneration in rats occurred equally well with human NPC grafts of spinal cord identity.
Immune suppressive autonomic reflexes in SCI
Creation of a sympathetic anti-inflammatory reflex due to profound plasticity within spinal autonomic circuitry may explain the onset of systemic immune suppression in patients with SCI.
In a mouse model of high SCI (T3) that resulted in profound splenic atrophy and leucopenia, trans-synaptic labelling from the spleen revealed an increase in excitatory interneurons that formed new synapses with sympathetic preganglionic neurons. This was not seen in control mice or a mouse model of T9 SCI.
Researcher Phillip Popovich (The Ohio State University Medical Center, Columbus, USA) and colleagues report that this led to a new intraspinal circuitry that was activated by a receptive field extending beyond the thoracic spinal segments that normally innervate secondary lymphoid tissues.
As a result, spontaneous activation of spinal interneurons by stimuli such as bladder and bowel filling resulted in exaggerated activation of neurons that innervate vasculature, viscera and lymphoid tissues, causing a sympathetic anti-inflammatory reflex.
The use of chemogenetics to target the specific gene signatures of the newly forming interneurons and silence signalling successfully prevented the immune suppressive reflex, however, reversing atrophy in the animals’ spleens and increasing white blood cell counts.
“Our model is clinically relevant; the application of similar techniques in humans could eliminate SCI-[immune depression syndrome] and improve quality of life for those living with SCI”, the researchers conclude in Nature Neuroscience.
By Lucy Piper
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