Every year in France, almost 170,000 people suffer a cranial or spinal cord injury. Nearly 10,000 of them are left with lifelong disabling disabilities, including paraplegia or tetraplegia in the case of spinal cord injuries.
Description of trauma
Lesions to the spinal cord are very rarely anatomical ruptures with loss of continuity, but rather contusions. Many research teams are working on this subject, but the clinical reality is that we do not currently know how to repair the spinal cord.
In the case of tetraplegia or paraplegia, the aim is to enable the severed or compressed spinal cord to function again, by restoring the continuity of the millions of axons that run through it.
A large number of research avenues have been explored in an attempt to improve protection of the spinal cord, i.e. the evolution and extension of the lesion after the trauma (secondary lesion of the spinal cord).
Research by the Paris Brain Institute
Claire Wyart's team is developing fundamental approaches to spinal cord repair using zebrafish for their exceptional regeneration capacities. She is seeking to understand how the nervous networks of the spinal cord are recruited to carry out a series of complex locomotor actions.
The spinal locomotor network (or rhythm-generating centre) of particular interest to the team enables us, for example, to walk without thinking about it once we have decided to move. This ability to maintain movement comes from the network's capacity to generate electrical oscillations. Various data (physiological, pharmacological and anatomical) have been used to understand how these oscillations are generated in vitro (outside a living organism). However, these approaches do not reveal whether discharges from a given subgroup of neurons are necessary and sufficient to generate movement.
To fill this gap, the team is studying the function of specific spinal cells in vivo in larval zebrafish. Although this animal model may seem far removed from humans, it offers decisive advantages for research aimed, in the long term, at repairing the spinal cord and restoring normal locomotion in disabled patients. The zebrafish nervous system evolves very rapidly, which saves time in understanding these mechanisms. What's more, the larvae are transparent, making them particularly well suited to optogenetics, a cutting-edge technique that uses light to trigger targeted neurons from a distance.
This new approach makes it possible to activate and deactivate sub-groups of neurons and determine their role in the animal's movement. It has made it possible to dynamically test the genetic role of an identified neuron type in the initiation and modulation of locomotor behaviour in an awake animal. The team's aim is to elucidate how sensitivity to movement contributes to locomotion. They recently discovered that, in addition to neurons that contact cerebrospinal fluid (CSFns), mysterious sensory neurons are located in the centre of the spinal cord. Their activation modulates the locomotion of the larva. This observation opens up a new field of investigation into the sensory interface between the spinal cord and the cerebrospinal fluid.
Professor Hugues Pascal-Moussellard is an orthopaedic surgeon at the Pitié-Salpêtrière Hospital, specialising in spinal column surgery. He is involved in research at the Paris Brain Institute in collaboration with Dr Claire Wyart. His research work aims to advance the problem of repairing myelin (the protective sheath that surrounds axons and enables nerve information to be transmitted) in patients with spinal cord injuries.
