Bonn. After spinal cord injury nerve fibers do not regenerate by themselves; loss of neuronal function up to complete paralysis is the consequence. When investigating new potential therapies, scientists are often confronted with an experimental problem: Neurons are embedded deep into the tissue of the spinal cord and thus difficult to access with microscopy methods. Scientists around Professor Frank Bradke, German Center for Neurodegenerative Diseases (DZNE), have now met this experimental challenge with the development of a new technology. In animal models, they treated the tissue of the spinal cord so that it became permeable to light. Using this treatment, they were able to investigate the regeneration process under the microscope much faster and far more accurately than it was previously possible. The work was carried out during Bradke’s research period at the Max Planck Institute for Neurobiology (Martinsried) in collaboration with researchers from the Vienna University of Technology and is now published in the prestigious journal Nature Medicine. Since July 2011, Bradke has been at the DZNE in Bonn.
Neurons of the central nervous system are surrounded by a myelin sheath. This sheath protects the nerve cells, but it also prevents their regeneration after injury. What are the factors that hamper regeneration and what can be done to get neurons to nonetheless bridge the lesion gap? These questions are subject to many scientific studies worldwide. Because the spinal cord – even that of mice – is too thick and opaque to investigate it as a whole in the microscope, the tissue was, until now, cut into thin sections prior to analysis. This is not only tedious but also error-prone, because inaccuracies can occur during the assembly of the resulting partial data.
Bradke and his team have developed a method by which the spinal cord of the mouse can be studied as a whole. To this end, the tissue is treated so that it becomes permeable to light. The water content of the tissue is replaced by compounds that refract light in a manner similar to the lipids and proteins of the tissue, so that the light can easily penetrate into the tissue. The researchers combined their method for tissue treatment with advanced microscopy technologies, such as the ultra-microscopy, in which the tissue is illuminated with a strong laser beam from the side.
With their new method Bradke and his colleagues studied the regeneration of neuronal fibers in mice up to one year after the spinal cord was severed. They showed that the neurons of the spinal cord not only show some initial sprouts but also occasionally produce extensions that can overcome the lesion. Nerve cells in the spinal cord are therefore not quite as resistant to regeneration as previously assumed. In addition, Bradke and his colleagues investigated neurons that were stimulated to regenerate by a certain methodical procedure and found that they could trace their trajectories with unprecedented accuracy. In further experiments, the researchers aim to investigate therapeutic options for spinal cord regeneration in more detail.
The enormous advances in cell biology in recent decades can to a large extent be attributed to the development of new microscopy technologies and methods. The development of Bradke and his colleagues is another important step forward in this respect. Moreover, the method is not limited to investigations of the spinal cord. Also other tissues can be rendered more accessible for microscopy with this methodology. It is conceivable, for example, to use the new technology for analyzing the network structure of the brain. This would then also be a valuable tool in the study of neurodegenerative diseases.
Ali Ertürk, Christoph P Mauch, Farida Hellal, Friedrich Förstner, Tara Keck, Klaus Becker, Nina Jährling, Heinz Steffens, Melanie Richter, Mark Hübener, Edgar Kramer, Frank Kirchhoff, Hans Ulrich Dodt & Frank Bradke. Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury. Nature Medicine, published online December 25, 2011. DOI: 10.1038/nm2600
Dr. Katrin Weigmann
German Center for Neurodegenerative Diseases (DZNE)
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