Zebrafish provide clues to healing human spinal cord injuries

Zebrafish have the extraordinary ability to completely regenerate their spinal cord after severe injury. However, how this natural healing process works has long been a mystery.

A new study has shown how zebrafish regenerate their spinal cord, offering hope for patients with spinal cord injuries. In humans, such injuries can lead to a lifelong loss of sensation and mobility.

Mayssa Mokalled and her team at Washington University School of Medicine have mapped the complex cellular process of spinal cord regeneration in zebrafish.

“We found that most, if not all, aspects of neuronal repair that we want to achieve in humans occur naturally in zebrafish,” said Mokalled.

The lead author added: “Our study has identified genetic targets that will help us promote this type of plasticity in the cells of humans and other mammals.”

Neurons play a key role

When the human spinal cord is injured, the damage is often irreversible and leads to paralysis. However, zebrafish defy this danger. Instead of dying, their damaged neurons undergo a dramatic transformation through altered cell functions.

In this way, the nerve cells survive the injury and even take on new functions to facilitate a faster healing process. They develop remarkable flexibility that allows them to form new connections and bridge the gap created by the injury.

“Neurons alone, without connections to other cells, do not survive,” said Mokalled.

“Our surprising observation is that strong neuronal protection and repair mechanisms emerge immediately after injury. We believe that these protective mechanisms allow neurons to survive the injury and then adopt a type of spontaneous plasticity – or flexibility in their functions – that gives the fish time to regenerate new neurons to achieve full recovery,” Mokalled explained in the press release.

In short, the researchers found that the ability of damaged neurons to adapt and change rapidly is critical for zebrafish spinal cord regeneration. It is this flexibility, not stem cells, that drives the healing process. Knocking out these neurons prevents complete healing, even when stem cells are present.

Development of treatment methods for spinal injuries

This suggests that these resilient neurons and not, as previously thought, stem cells are the key to regeneration.

Spinal cord injuries in humans and other mammals cause a toxic response that kills neurons and hinders recovery.

The researchers stress that this toxic environment may explain why stem cell treatments have not worked for spinal cord injuries. The findings suggest that the focus of future therapeutic drugs should be on preventing neuron death.

Researchers believe that this regenerative ability, albeit inactive, may be present in mammalian nerve cells. The identification of these genes offers great hope for the development of new treatment options.

This study focused only on neurons, but spinal cord healing is complex and involves other cell types as well. Next, the team plans to create a detailed cell atlas to understand the role of other cell types in this healing process.

The study was published in the journal Nature communication.