Grant: Project Grant

Stroke refers to brain damage due to blocked blood flow in the brain. The spinal cord can "rewire" itself to help stroke survivors recover movement. Sadly, recovery is not complete. Incomplete recovery may be because the spinal cord rewires only for a short period of time after stroke. A protein called pleiotrophin (PTN) is a growth factor naturally produced by the body. PTN is known to increase the growth of new connections between brain cells. We have recently shown in rats that injecting PTN into the spinal cord after stroke significantly improves recovery. More data in animal models of stroke such as this are needed to confirm PTN therapy can improve recovery. Additionally, the role of PTN in the recovery that occurs naturally after stroke or recovery due to physical therapy needs to be defined. Here, we will use animal models of stroke to determine how the levels of PTN in the brain and spinal cord change in the weeks that follow a stroke. Additionally, we will block PTN in the spinal cord to show its role in the rewiring and recovery that follows stroke. Finally, we will increase PTN signaling in the spinal cord and determine if this can improve recovery make physical therapy more effective after stroke. We predict that: (1) PTN levels in the spinal cord will be highest early after stroke, and return to normal levels at the same time that recovery stops. (2) Blocking PTN levels in the spinal cord will make recovery worse. (3) Increasing PTN signaling will improve recovery even long after the stroke has occurred. We believe PTN is an exciting new stroke therapy. By defining how PTN contributes to recovery from stroke, we hope to find new ways to reduce disability in stroke survivors. Most stroke survivors have some degree of disability, and this research may lead to methods to reduce disability even years after the stroke.