Grant: Operating Grant

Injuries to the spinal cord results in permanent paralysis and loss of sensation because of the limited ability of damaged nerve cells in the spinal cord to be replaced with new ones, and the limited ability to regenerate or regrow damaged nerve fibers. There are about 85,000 people in Canada with spinal cord injury (SCI), with 4500 new cases each year. About half of these new cases occur in young people, leading to a lifetime of being paralyzed. At present there are no effective treatments. There is therefore a great need to develop treatments to improve outcome after SCI. Spinal cord injuries trigger a strong inflammatory response at the site of injury. This response involves a cell called the macrophage that serves to clear the injury area of damaged cells. However, macrophages in the injured CNS can be toxic, kill cells, and cause additional tissue damage and functional loss. Under other conditions, macrophages can also have beneficial effects for tissue repair. Preventing the toxic effects of these macrophages while preserving their beneficial effects will therefore aid recovery after spinal cord damage. Recent studies in the field of macrophage biology indicate that these cells can adopt either a pro-inflammatory M1 form or a pro-repair M2 form, referred to as polarization states. This proposal is designed to identify molecules that control this type of macrophage polarization in the damaged spinal cord, and test and develop ways to alter their polarization state to promote healing and repair after SCI. These studies will have important implications for the development of treatments for spinal cord injury and may also benefit other neurological conditions in which inflammation occurs such as ALS and Alzheimer's disease.