Stroke is the fourth leading cause of death and the leading cause of disability in the world. Unfortunately, treatment options for stroke remain limited to pharmacologic or mechanical revascularization in select patients. Despite decades of preclinical research, efforts to develop additional therapeutic strategies have uniformly failed, due in large part to an incomplete understanding of the mechanisms of ischemic brain injury as well as to inherent limitations of preclinical models and subsequent clinical trial design.
The ultimate goal of the Ducruet Laboratory is to develop a successful therapeutic strategy for stroke patients. To this end, we utilize both in vitro and in vivo experimental models in an effort to delineate the cellular and molecular mechanisms underlying ischemic brain injury.
Our work focuses on the study of complement cascade activation, which occurs in response to cerebral ischemia. The complement cascade is a central component of the innate immune response that incorporates more than 30 serum proteins, membrane bound receptors, and regulatory proteins. Complement’s functions in host defense and inflammation are mediated through the sequential activation and proteolytic cleavage of a series of serum proteins. Our group and others have shown that complement also plays a critical role in acute inflammatory brain injury in stroke.
Recently, a number of additional roles of complement in postischemic recovery and repair also have been described. Understanding the myriad parallel and overlapping functions of complement activation in ischemic brain is therefore essential to developing a successful therapeutic strategy modulating complement in stroke.
Our laboratory uses multiple clinically relevant experimental models of stroke and has access to tissue samples from human stroke patients. We are, therefore, ideally positioned to translate breakthroughs at the bench into the clinic, as well as to bring clinical observations and findings from the study of human patients to the bench, guiding future preclinical efforts.