Grant: Project Grant

BACKGROUND: Platelets are small cells that circulate in blood. They form a plug to prevent bleeding in case of injury in the blood vessel. Platelets then take on a role in wound healing. Platelets can discharge many proteins around the wound, including growth factors that help the vessel grow new cells to close the wound. Surprisingly, platelets also contain brain growth factors, which they also discharge when they respond to injury. There is 100 times more brain growth factors released by platelets than from brain cells. However, what brain growth factors do in the blood vessels remains unknown. WHAT WE HAVE DONE: We have isolated platelets from the blood of healthy volunteers to study their ability to release a specific brain growth factor named the brain-derived neurotrophic factor (BDNF). We have found that platelets release large amounts of BDNF, as well as its parent molecule proBDNF. We have also found that both BDNF and proBDNF are able to stimulate platelets to stick together, form a clot and release more of their cargo. We do not know how BDNF and proBDNF act on platelets or on blood vessels. WHAT WE WILL DO: We will identify which pathways BDNF and proBDNF use to induce clot formation. We will block different pathways to determine which ones are the most important. We will pinpoint which receptors (locks) respond to BDNF and proBDNF (keys). Taken together, these experiments will allow us to understand the biology of brain growth factors outside the brain. POTENTIAL BENEFITS: By better understanding how platelets respond to brain growth factors, we will be able to encourage platelet to release of their useful cargoes and help vessels heal. This might be particularly important in the vessels that nourish the brain, where damaged blood vessels could lead to stroke and dementia. Platelets may be a new avenue of treatment for these crippling diseases.