Spinal cords, when damaged, can rarely repair themselves due to the excessive response of the immune system. For instance, it can create everlasting scar tissue that prevents nerve fibers from reconnecting and stabilizing. Researchers have discovered how zebrafish can control inflammation to recover the spinal cords, and, in return, revolutionize studies of regenerative medicine.
A new research study, published in the Journal of Neuroinflammation, has identified an immune mechanism that can regenerate damaged spinal cords. Scientists from the Becker group at the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology and the University of Edinburgh studied a specific group of immune cells that restrains the inflammatory response and supports conditions to recover movement.
The immune system contains a variety of cell types that contribute to the recovery of spinal cords. Neutrophils are among the first cells to reach impaired tissue. Previously, researchers examined these cells to be in control of removing debris from the injury site. One subgroup of neutrophils is a signaling molecule named IL-4. The molecule alerts additional immune cells to reduce inflammation before the injury is worsened.
The study examined the process neutrophils and IL-4 have in larval zebrafish by disabling these cells. The results included the overproduction of highly inflammatory proteins, which, in return, created the inability to regrow nerve fibers and loss of normal movement. Afterwards, the researchers artificially added IL-4 molecules directly to the injury area. Although the neutrophils were absent, inflammation subsided, and the spinal cords were able to regenerate completely. The research demonstrated that the IL-4 molecules could execute the essential signaling functions normally provided by immune cells.
Professor Thomas Becker, who led the study, elaborates how, “For the first time, we have shown that neutrophils play a massive, active role in successfully repairing a spinal cord. They aren’t just there to clear away debris; they act like conductors that tell other immune cells to return to a harmonious rhythm.” He concludes that “Without them, the immune system locks into a destructive cycle and prevents healing. By using the IL-4 molecule, the neutrophils smooth out the inflammation, allowing the delicate nerve fibers to grow right through the injury zone.”
The researcher’s findings indicate that successful spinal cord regeneration relies on the timing and intensity of the immunity provided. The debate over why zebrafish can repair spinal cord damage while humans cannot remains a major challenge. In people, the immune system’s response after injury often causes permanent damage within the central nervous system. Zebrafish offer insight into the precise process of a regulated immune system that supports nerve regeneration. The key finding of IL-4 molecules provides crucial information to humans; however, it does not determine whether human immune cells can respond similarly to zebrafish. “Of course, the question is to what extent our results apply to humans. It remains to be seen if IL-4 plays a similar role in humans and whether it can finely balance the inflammation allowing for better healing at the injury site,” explains Xiaobo Tian, who contributed to the study. Moreover, Tian concludes, “It is definitely a very promising avenue for future studies in humans.”
