Research

Basic Science Research

The primary focus of our basic science research is on the pathophysiology of cerebral aneurysms. An aneurysm is a focal weakening of a blood vessel in the brain which leads to vessel enlargement or bulging. In some patients the aneurysm may grow leading to further vessel damage and rupture resulting in a devastating form of stroke. Therefore, many patients are treated to help stabilize the aneurysm before it ruptures. Our research aims to understand the molecular and cellular mechanism which leads to cerebral aneurysm formation, growth, and rupture and to investigate new avenues for cerebral aneurysm treatment. We have several ongoing research projects:

1. Endothelial and vascular smooth muscle cell dysfunction and death are associated with cerebral aneurysm formation, growth, and rupture. Although multiple inflammatory cascades are implicated in inducing vascular smooth muscle dysfunction and death, there is relatively little known about the mechanisms leading to endothelial cell dysfunction. Therefore, this study aims to understand the role of inflammatory pathways in endothelial cell dysfunction and how this relates to aneurysm progression.
2. An extensive body of clinical and preclinical data demonstrates that cigarette smoking enhances the risk of aneurysm formation, rupture and treatment failure. However, the mechanisms by which smoking increases the risk of cerebral aneurysms and treatment failure is not fully defined. Smoking is known to induce cellular dysfunction and death of endothelial and vascular smooth muscle cells, the two primary cellular components of the blood vessel wall. We have previously shown that cigarette smoke enhances vascular smooth muscle cell phenotypic switching and death resulting in increased rates of aneurysm rupture. However, it is not known if cigarette smoke induces endothelial cell dysfunction which in turn contributes to the enhanced aneurysm formation and rupture observed in patients who smoke. The goal of this project is to determine the effects of cigarette smoke on endothelial function and how this may contribute to aneurysm progression.
3. Endovascular treatment of cerebral aneurysm has become the first line treatment modality for both unruptured and ruptured aneurysms. However, endovascular treatment can fail in some patients thereby requiring retreatment which increase the patient’s costs, morbidity, and mortality. The reason for treatment failure is complex but essentially stems from the inability to promote cellular growth across the aneurysm neck thereby healing the parent artery. The goal of this study is to determine if we can increase aneurysm obliteration by enhancing neo-endothelialization of aneurysm occlusion devices.

Clinical Research

Clinically we study all forms of cerebrovascular disease, such as ischemic and hemorrhagic stroke, vascular malformations, cerebral aneurysms, and others. The goal of this research is to work with medical device companies in the testing of novel neurovascular devices and to allow an avenue for the translation of preclinical findings into the clinic. We have several ongoing projects.

1. The importance of developing a treatment for stroke cannot be overstated; stroke is a leading cause of death and is the number one cause of disability in the United States. Despite this fact, there has been little advancement in the development of therapeutic treatments for ischemic stroke. Remote ischemic preconditioning is a neuroprotective mechanism in which a brief non-damaging ischemia-reperfusion event protects against a subsequent damaging ischemic attack. Preclinical data demonstrates the neuroprotective effectiveness of remote ischemic preconditioning. However, the clinical translatability of remote ischemic preconditioning is less clear. In this study we are examining the ability of remote ischemic preconditioning to prevent procedurally induced brain infarct damage in patients undergoing endovascular repair of unruptured cerebral aneurysms.
2. In this clinical study we are determining if treating patients with the mTOR inhibitor sirolimus alters gene and protein expression in aneurysm tissue. If successful, this study can be expanded to determine the therapeutic potential of sirolimus for cerebral aneurysm treatment.