CST Regeneration in the Chronic Injury Setting

Most of our readers know that the "Corticospinal Tract Regeneration Project" has been the focus of the Steward Research Group for years, and for the last 5 years has involved a multi-investigator collaboration that has been following up on a paper the team published in 2010. The original paper, published in Nature Neuroscience, showed that it was possible to induce regeneration of the corticospinal tract (CST) following spinal cord injury by deleting a gene called phosphatase and tensin homolog (PTEN). The latest papers from the Steward lab, published in 2014 and earlier this year, showed that CST regeneration was accompanied by recovery of motor function. (See next article: PTEN Deletion Post SCI Regeneration and Recovery by Sam Maddox)

In a new breakthrough, our collaborator Dr. Kai Liu, who was first author on the Nature Neuroscience paper and now has his own lab at Hong Kong University, published a very important paper showing that is possible to induce CST regeneration in the chronic setting either 4 months or 1 year after a spinal cord injury!

The paper appeared in the July issue of the flagship journal of our field, the Journal of Neuroscience, and was featured on the cover. In the study, Dr. Liu used the same genetic deletion strategy that was used the original paper. Mice received spinal cord injuries and then 1 year later, received an injection of a viral -based vector into their cortex, which produces a protein that deletes PTEN from the nerve cells that give rise to the CST. After deleting PTEN, CST axons regenerated past the injury and formed new connections. The discovery that regenerative ability can be rebooted even one year after an injury greatly extends the window of opportunity for regenerating connections in the injured spinal cord. Next steps will be to determine if the regeneration is accompanied by reversal of paralysis.