Zebrafish’s unique healing raises hope for human spinal cord injury treatment

Zebrafish are known to possess the extraordinary ability to fully regenerate their spinal cords following serious damage. However, how this natural healing process works has long been a mystery.

A new study has uncovered how zebrafish regenerate their spinal cords, offering hope for human spinal cord injury patients. In humans, such injuries may result in lifelong loss of sensation and mobility.

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

“We found that most, if not all, aspects of neural repair that we’re trying to achieve in people occur naturally in zebrafish,” said Mokalled.

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

Neurons play a key role

When a human spinal cord is injured, the damage is often irreversible, leading to paralysis. But zebrafish defies the odds. Their damaged neurons, rather than dying, undergo a dramatic transformation through altering cellular functions.

This way, neuron cells survive the injury and even take on new functions to facilitate a faster healing process. They develop remarkable flexibility, allowing them to form new connections and bridge the gap created by the injury.

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

“The surprising observation we made is that there are strong neuronal protection and repair mechanisms happening right after injury. We think these protective mechanisms allow neurons to survive the injury and then adopt a kind of spontaneous plasticity — or flexibility in their functions — that gives the fish time to regenerate new neurons to achieve full recovery,” explained Mokalled in the press release.

In a nutshell, the researchers discovered that the ability of damaged neurons to swiftly adapt and alter is critical for zebrafish spinal cord regeneration. This flexibility, rather than stem cells, drives the healing process. Disabling these neurons hinders complete healing, even when stem cells are present.

Developing spinal injury treatments

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

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

The researchers highlight that this toxic environment might explain why stem cell treatments haven’t worked for spinal cord injuries. According to the findings, the key focus for future therapeutic medicines should be on preventing neurons from death.

Researchers believe that this regenerative ability, while dormant, could potentially be present in mammalian neurons. The identification of these genes holds great promise for creating new treatment options.

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

The study was published in the journal Nature Communications.