Timing found to be crucial for spinal cord repair in zebrafish
The healing of the spinal cord depends on carefully timed interactions between injured nerve cells and their surrounding environment, according to a new study published in Science Advances by researchers at Karolinska Institutet.
Spinal cord injury often leads to long-term disability because damaged neurons in humans have a limited ability to recover. To better understand what successful repair requires, researchers examined adult zebrafish, a vertebrate species that can naturally regenerate its spinal cord.
“We discovered that neurons that are physically damaged by injury do not simply shut down or die. Instead, they undergo temporary, reversible changes in their activity and in how they communicate with other neurons,” says corresponding author Konstantinos Ampatzis, principal researcher at the Department of Neuroscience.
At the same time, the extracellular matrix – the supportive mesh-like structure around cells – adapts in a controlled way. One key component, chondroitin sulphate proteoglycans (CSPGs), increases briefly following the injury. Together, these findings show that spinal cord healing is not driven by a single factor, but by a carefully timed interaction between neurons and their microenvironment.
Spinal cord injury is devastating because, in humans and other mammals, damaged neurons have a very limited ability to recover. Many experimental treatments aim to “remove barriers” to regeneration, especially by breaking down the extracellular matrix.
A dual role for the surrounding tissue
Although CSPGs are often viewed as an obstacle to regeneration, the researchers found that they play a double role. Early after injury, they stabilise and protect damaged neurons. Later, they support long-term regrowth. When CSPGs were reduced too early using an enzyme, initial healing accelerated but long-term regrowth and movement recovery were impaired.
“Our results indicate that timing is essential. Molecules that appear to limit recovery at one stage may be important for repair at another. Understanding this balance could help guide future treatment strategies,” says Konstantinos Ampatzis.
The team used a multidisciplinary approach to study adult zebrafish after complete spinal cord injury. Through electrical recordings and imaging, they tracked changes in spinal neurons and the surrounding structure, especially chondroitin sulfate proteoglycans. By applying an enzyme to modify this structure, they evaluated its impact on healing and swimming ability, ultimately creating a timeline of neuron and environment recovery.
What happens now?
The next step is to identify which cells generate the extracellular matrix after injury and how this process is controlled. The roles of neurons, glial cells, and immune cells remain unclear. Researchers aim to fine-tune neuronal plasticity and matrix remodeling, potentially enabling therapies that protect neurons early and promote later regeneration for spinal cord injury treatment.
See the study for funding and any reported conflicts of interest.
Publication
Time-dependent adaptations of damaged neurons and their microenvironment in the regenerating adult zebrafish spinal cord, Leslie Lafouasse, Konstantinos Koutsogiannis, Yu-Wen E. Dai, Lisa Del Vecchio, Andrea Pedroni, Dimitrios Tsagkogiannis, Judith Habicher, Konstantinos Ampatzis, Science Advances, 6 Mar 2026, Vol 12, Issue 10, doi: 10.1126/sciadv.aea2882.