Scarring in spinal cord injuries
Spinal cord injuries are among the most challenging neurological conditions, often resulting in permanent loss of motor and sensory function. A critical issue in treating these injuries is the formation of scar tissue. While initially protective, scar tissue later becomes a barrier that prevents nerve regeneration.
A recent study, led by Dr Wendy Yue, a former Croucher Fellow at the University of California, San Francisco, during her time in David Julius’ lab, has provided valuable insights into how to manage this scarring process to improve recovery outcomes. The study has just been published in Nature. Croucher News caught up with Yue recently to find out more about her research.
“The spinal cord plays a vital role in the central nervous system, transmitting sensory information to the brain and coordinating motor responses,” Yue explains. “When the spinal cord is injured, scar tissue forms to protect the damaged area, but it also creates a physical and chemical barrier that prevents nerves from regrowing and reconnecting.” The challenge, therefore, is to control this process to retain the protective function of scar tissue without hindering long-term recovery.
Yue’s research revealed a key role for a kappa opioid signalling pathway in regulating scar formation. This pathway, normally active in the body, becomes disrupted following spinal cord injury. By using a drug to reactivate this pathway, Yue and her colleagues were able to reduce scar tissue formation, providing proof-of-concept that this process can be modulated pharmacologically with kappa opioids.
“What’s exciting is that kappa opioids are non-addictive peptides, offering a promising way to target this pathway without the typical side effects associated with opioid treatments,” Yue says. The next step is to develop a more dynamic approach, which will involve further research into the timing and dosage of drug application.
The kappa opioid pathway involves a group of neurones located near the central cavity of the spinal cord, which is filled with cerebrospinal fluid (CSF)—the clear liquid that cushions the brain and spinal cord and supports neural function. These neurones, which resemble sensory cells, are positioned to potentially detect changes in the CSF.
“Initially, we aimed to explore the sensory functions of these neurones,” Yue recalls. “But we soon realised that they might play a critical role in injury response, which led us to shift our research focus.”
This shift has inspired Yue’s current exploration into fluid-neurone interactions, which could have broader implications beyond spinal cord injury recovery. Yue explained that the brain has two major fluid systems—the blood and the CSF—but communication between them is limited by the blood-brain barrier.
“While the blood-brain barrier protects the brain from harmful substances, it also restricts the passage of chemical signals,” Yue told us. “I’m particularly interested in regions where this barrier is more permeable, as these areas often play key roles in sensory or secretory functions.”
Understanding how chemical exchange occurs across these regions could also advance methods for drug delivery to the brain, addressing one of the biggest challenges in treating neurological diseases.
Driven by curiosity, Yue reflects on the fundamental questions that guide her research. “I’m motivated by understanding how things work, especially how neurones interact with their environment,” she explains. “This is fundamental to how animals, including humans, communicate with the external world and connect with our surroundings.”
As she continues to build her new independent lab at the University of California, San Francisco, Yue is looking to explore fresh ideas and welcome like-minded students and postdocs to join her in uncovering new insights into brain physiology. She is excited by the prospect, despite the uncertainties that come with research.
“You hope that whatever you find will be useful. But with science, it's difficult to predict what the final outcome of the project will be.”
You can read Yue’s Croucher profile here.