This seminal study, published in this week's Proceedings of the National Academy of Science, identifies key elements in the body's reaction to spinal injury, critical information that could lead to novel therapies for repairing previously irreversible nerve damage in the injured spinal cord. Very little is known about why, unlike a wound to the skin for example, the adult nervous system is unable to repair itself following spinal injury. This is in contrast to the developing brain and non-mammals which can repair and regenerate after severe injuries. One clue from these systems has been the role of stem cells and their potential to develop into different cell types.
"Because of their regenerative role, it is crucial to understand the movements of stem cells following brain or spinal cord injury," says Dr. Philip Horner, co-lead investigator and neuroscientist at the University of Washington. "We know that stem cells are present within the spinal cord, but it was not known why they could not function to repair the damage. Surprisingly, we discovered that they actually migrate away from the lesion and the question became why - what signal is telling the stem cells to move."
The researchers then tested numerous proteins and identified netrin-1 as the key molecule responsible for this migratory pattern of stem cells following injury. In the developing nervous system, netrin-1 acts as a repulsive or attractive signal, guiding nerve cells to their proper targets. In the adult spinal cord, the researchers found that netrin-1 specifically repels stem cells away from the injury site, thereby preventing stem cells from replenishing nerve cells.
"When we block netrin-1 function, the adult stem cells remain at the injury site," says Dr. Tim Kennedy, co-lead investigator and neuroscientist at the Montreal Neurological Institute of McGill University. "This is a critical first step towards understanding the molecular events needed to repair the injured spinal cord and provides us with new targets for potential therapies."
This study was funded by the Craig H Nielsen Foundation and the National Institutes of Health.
About the MNI- The Montreal Neurological Institute is a McGill University research and teaching institute, dedicated to the study of the nervous system and neurological diseases. Founded in 1934 by the renowned Dr. Wilder Penfield, the MNI is one of the world's largest institutes of its kind. MNI researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. The MNI, with its clinical partner, the Montreal Neurological Hospital (MNH), part of the McGill University Health Centre, continues to integrate research, patient care and training, and is recognized as one of the premier neuroscience centres in the world. At the MNI, we believe in investing in the faculty, staff and students who conduct outstanding research, provide advanced, compassionate care of patients and who pave the way for the next generation of medical advances. Highly talented, motivated people are the engine that drives research - the key to progress in medical care.