How Hydrogen Peroxide Can Accelerate Nerve Repair

A new study has exploited the incredible regenerative capacity of the zebrafish to explore how hydrogen peroxide might be used to help repair wounds and damaged nerves.

The regenerating fish

The research, published in Proceedings of the National Academy of Science (PNAS), was led by researchers at the University of Miami, including senior author Sandra Rieger. Rieger’s model of choice is the zebrafish (Danio rerio), a species of striped fish just a few centimeters in length that possess the uncanny ability to regenerate parts of their nervous system after damage.

When working as a postdoctoral researcher at the University of California, Los Angeles, Rieger discovered that axons – the long projections of neurons that transmit electrical signals – in the skin of zebrafish were regenerated via a mechanism dependent on hydrogen peroxide (H₂O₂).

"It was a great discovery, but at the time we did not know the exact molecular mechanisms that drove nerve regeneration after injury,” said Rieger, now an assistant professor at the University of Miami, in a press release.

In their latest study Rieger and her team took a closer look at how H₂O₂ mediated its regenerative action. After labeling proteins in the zebrafish with fluorescent tags, they used a technique called time-lapse imaging to study the regeneration process. “Time-lapse imaging provides a detailed view of the biological processes and relationships between nerves and skin, as well as how these interactions lead to regeneration," Rieger explained.

A vital role for oxidases

Rieger and her team knew from previous study that proteins called NADPH oxidases were critical to the process of regeneration. The new paper showed that separate oxidases, signaling from skin and nerve cells respectively, work together to mediate healing in response to H₂O₂.

The study found that hydrogen peroxide reacts to epidermal growth factor receptors (EGFR) in the skin. This reaction is essential for skin remodeling and aids nerve regrowth into the wound. “This is vital for the restoration of the skin,” said Rieger. 

"However, we discovered that if hydrogen peroxide is not present in neurons, nerve endings also cannot regenerate," explained Rieger. "It appears that both neurons and skin require hydrogen peroxide to coordinate the regeneration of their nerve endings."

Neuronal healing after injury, while a routine process in zebrafish, is rare in humans and has proved a significant obstacle in regenerative medicine. The new findings, write the authors, “could aid in therapeutic development for patients with wound healing and axon regeneration defects or in the prevention of axon degeneration.”

Reference:  Cadiz Diaz A, Schmidt NA, Yamazaki M, Hsieh CJ, Lisse TS, Rieger S. Coordinated NADPH oxidase/hydrogen peroxide functions regulate cutaneous sensory axon de- and regeneration. PNAS. 2022;119(30):e2115009119. doi: 10.1073/pnas.2115009119

This article is a rework of a press release issued by the University of Miami. Material has been edited for length and content.