Zebrafish are small fish from the minnow family found natively in India. At only five centimeters long (about the size of a golf tee), they might not jump to mind as something used to study human health and disease. However, many unique features of the zebrafish make them a great model organism for biologists. One really cool aspect of zebrafish biology is that since zebrafish are transparent, the biology occurring within their living cells can be visualized in vivo using fluorescent molecules.

The similarities between zebrafish and human genes have led to zebrafish studies related to a range of human diseases. However, a new study published in Biophysical Journal (DOI:https://doi.org/10.1016/j.bpj.2019.10.044) focused on understanding key differences in the spinal cords of zebrafish and humans. In mammals, traumatic spinal cord injury (SCI) permanently impairs the normal exchange of information between the brain, the peripheral nervous system, and the periphery of the body. The result of this impairment is paralysis. Yet in zebrafish, a comparable traumatic spinal cord injury does not lead to permanent paralysis, but rather the fish can repair the spinal cord damage and regain function within six to eight weeks after the injury.

The permanent loss of motor function after SCI in mammals is thought to be related to scar tissue, referred to as the glial-fibrotic scar, that forms during the healing process. It is thought that this scar tissue can mechanically and biochemically prevent cellular growth and signaling following the injury, which leads to permanent impairment. However, the specific details regarding this process are still not fully understood. Given that zebrafish have the unique ability to repair spinal cord damage, Stephanie Möllmert and colleagues aimed to study the mechanical changes that occur during the SCI recovery process.

Using a method called atomic force microscopy, the authors of this study were able to systematically determine the mechanical stiffness of the spinal cord tissue before and after SCI at distinct regions along the zebrafish spine. The spinal cord contains regions referred to as “gray matter” and “white matter,” each of which contains different types of cells that play specific roles in neural processes. To establish the experimental system, the researchers first investigated spinal tissue from healthy fish that had not undergone SCI. This analysis revealed that the stiffness of gray matter regions of the spinal cord was much greater than the stiffness of the white matter regions. Importantly, these experiments provided baseline measurements in healthy fish which then allowed comparison with stiffness measurements following injury.

To investigate tissue stiffness during zebrafish recovery from spinal cord injury, the authors performed the same atomic force microscopy tissue indentation analyses on spinal tissue obtained following spinal cord injury. They monitored the change in mechanical stiffness over time during the injury recovery period. While it could be hypothesized that stiffer tissue may impede cellular recovery, surprisingly, the results of this work suggested the opposite. The authors found that during the recovery period of two to four weeks post injury, both the gray and white matter regions of the spinal tissue became stiffer than pre-injury. Interestingly, within this time frame, the distinct stiffness differences between the gray and white matter regions were lost and these regions exhibited similar stiffness. By six weeks post injury, as the tissue sections reached homeostasis, the gray and white matter regions regained their stiffness differences from the pre-injury time period as the white matter stiffness declined. A graphical depiction of the hypothesized process describing the mechanobiology of spinal tissue healing can be seen in Figure 6 in the article by Möllmert et al.

In summary, this work demonstrates the role that mechanical tissue properties play during the critical healing period from spinal cord injury in zebrafish. The results of this work suggest that tissue stiffening during recovery, while previously thought to impede neuronal regrowth, may in fact be an important driver of successful healing. These important findings indicate that tissue mechanics strongly influence spinal cord healing and open several doors for future study into spinal cytoarchitecture.

- Abigail Powell, Biophysical Journal Social Media Contributor