Grant: Operating Grant

Injury to the central nervous system (CNS), which includes the brain and spinal cord results in permanent functional loss of because of the inability of the CNS nerve cells to regenerate. CNS injuries trigger a robust inflammatory response at the site of injury but a weak and delayed response away from the lesion. This immune response involves a cell called the macrophage that serves to remove damaged cells. However, macrophages in the injured CNS can be toxic, kill cells, and cause additional tissue damage and functional loss. Macrophages on the other hand also have beneficial effects for tissue repair. Preventing the toxic effects of these macrophages while preserving their beneficial effects will therefore aid recovery. In regions away for the lesion, the macrophage response is very poor; as a result damaged nerve fibers and their covering sheath called myelin are removed very slowly. The slow removal of myelin has important consequences for subsequent nerve regeneration because myelin contains molecules that prevent growth of damaged nerve fibers. In addition, it is important to understand how inflammation is terminated. This proposal is designed to identify molecules that control these macrophage responses. These studies will have important implications for the development of treatments for spinal cord injury and other neurological conditions in which inflammation occurs such as stroke and brain trauma.