SPINAL CORD INJURIES

Each year in France, nearly 170 000 people are victim of brain or spinal cord injury. Almost 10 000 of them keep impairing disabilities for life, including paraplegia or tetraplegia in the case of spinal cord injuries.
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TRAUMA DESCRIPTION

Spinal cord injuries are very rarely anatomical fractures with lost continuity, but rather bruises. Many research teams are working on this topic, however clinical reality is that for now we can not repair the spinal cord.

In cases of tetraplegia or paraplegia, the objective is to restore the severed or compressed spinal cord functioning, repairing the continuity of the million axons crossing it.

A great many research directions have been experimented to try to improve spinal cord protection, namely, lesion evolution and extension after trauma (secondary spinal cord injury).

ICM RESPONSES

Claire Wyart’s team develops basic approaches for spinal cord repair, using zebrafish for its exceptional regeneration capabilities. It is trying to understand how spinal cord nerve networks are recruited to set up a series of complex locomotor actions.

The spinal locomotor network (or rhythm generating center) in which the team is particularly interested allows – for example – to walk without thinking once the decision to move is made. This capacity to support movement comes from the network’s ability to generate electrical oscillations. Different data (physiological, pharmacological, and anatomical) were used to understand how these oscillations are generated in vitro (outside a living organism). However, these approaches do not reveal whether a given neuron sub-group’s discharges are necessary and sufficient to generate movement.

To remedy these shortcomings, the team is studying specific spinal cell function in vivo in the zebrafish larvae. This animal model might seem distant to man, but it offers key benefits for research aiming to, in the long term, repair the spinal cord and restore normal locomotion in disabled patients. In such cases, the zebrafish’s nervous system is evolving very quickly, saving time for understanding these mechanisms. In addition, the larvae are transparent, which makes them particularly suited to optogenetics, cutting-edge technique enabling to remotely trigger through light targeted neurons.

This new approach allows to activate and deactivate neuron sub-groups and determine their role in the animal’s movement . It has been used to test dynamically the genetic role of an identified type of neuron in the initiation and modulation of an awakened animal’s locomotor behaviour. The team aims to elucidate how sensitivity to movements contributes to locomotion. It has recently discovered that in addition to neurons contacting the cerebrospinal fluid (CSFns), mysterious sensory neurons were located at the center of the spinal cord. Their activation modulates larval locomotion. This observation opens a new field of investigation on the sensory interface between the spinal cord and the cerebrospinal fluid.

Professor Hugues Pascal-Moussellard is an orthopedic surgeon at the Pitié-Salpêtrière hospital, specialised in spine surgery. He participates in research at the ICM in collaboration with Dr. Claire Wyart. His work aims to advance the myelin repair problem (protective sheath surrounding axons and allowing nerve information transmission) in patients with spinal cord lesions.