Grant Recipients

The Aneurysm and AVM Foundation is pleased to announce the recipients of the 2020 Cerebrovascular Research Grant Awards. We selected two researchers whose scientific projects showed the greatest potential to improve our understanding of cerebrovascular diseases.

Research Study: Evaluating the use of Remote Ischemic Preconditioning in Patients Undergo Endovascular Repair of Brain Aneurysms

Primary Investigator: John W. Thompson, Assistant Scientist, Neurological Surgery, UMCVI Director of Basic Science Research, University of Miami, Miller School of Medicine

Background: Cerebral aneurysms are common with a prevalence of 2-3% in the general population and exceeding 19% in high-risk populations. Cerebral aneurysm rupture produces a devastating form of stroke resulting in high rates of mortality and morbidity. Endovascular treatment of cerebral aneurysms is becoming the first-line treatment modality for both ruptured and unruptured CA. However, procedures in which catheters are introduced into the cervical carotid arteries commonly dislodge embolic materials that may lead to ischemic damage of varying frequency and severity.

A majority of patients undergoing endovascular aneurysm repair suffer from procedurally-induced infarcts, which are typically small-volume lesions, however some of these infarcts are immediately clinically evident as motor or sensory deficits or neurocognitive impairment. Other infarcts are clinically silent in the short-term but may manifest in long-term consequences such as early onset vascular dementia, and Alzheimer’s Disease. There are currently very limited treatments to reduce the risk of embolic infarcts during endovascular procedures.

Dr. Thompson believes remote ischemic preconditioning (RIPC) might be a key strategy in reducing the number of procedurally induced embolic infarcts. RIPC has been used for protection against both ischemic and reperfusion injury throughout the body, however it has never been used for protection against both ischemic and reperfusion injury throughout the body. Given the high frequency of embolic infarcts occurring during aneurysm repair and the potential for these to induce neurological alterations, this proposal will test this novel therapy to directly address this unmet need in patients undergoing endovascular aneurysm repair.

Research Objective: The goal of Dr. Thompson’s research is to define the molecular events behind cerebral aneurysm formation, growth and rupture and to develop novel medical therapies for the successful treatment of cerebral aneurysm patients. Currently, there are very limited medical therapies to prevent or reduce this issue in endovascular treated patients, so this study will investigate the potential of remote ischemic preconditioning as a therapeutic intervention for endovascular procedure induced embolic ischemic events.

Outcomes: With this grant from The Aneurysm and AVM Foundation, Dr. Thompson and his team will conduct their research to contribute to a better understanding of the efficacy of RIPC in the prevention of endovascular induced embolic infarcts as well as the mechanisms through which RIPC may lead to neuroprotection. He hopes that the positive impact of this research can enhance our understanding of RIPC neuroprotection and will give clinicians a new medical therapy to better patient outcomes following endovascular treatment of cerebral aneurysms.

Source: John W. Thompson, Assistant Scientist, Neurological Surgery, UMCVI Director of Basic Science Research. This research summary has been adapted and edited from Dr. Thompson’s research proposal.

Research Study: Neutrophil Infiltration in Coiled Aneurysm Healing: Adjuvant IL-17 Blockade

Primary Investigator: Koji Hosaka, Associate Scientist, University of Florida Division of Sponsored Programs

Background: Cerebral aneurysms affect up to 5% of the population. When aneurysms rupture, they cause devastating subarachnoid hemorrhage (SAH), which accounts for 5% of strokes and has an estimated mortality of 50%. Current treatment options to prevent rupture or rebleeding include surgery (craniotomy and clipping) or endovascular treatment (coiling or flow diversion stenting). Endovascular coiling appears to be safer than surgery for unruptured and ruptured aneurysms, however, coiling is associated with up to 44% incomplete treatment.

Based on surgical/autopsy studies, durable cerebral aneurysm healing occurs when a durable tissue plug containing immune cells, collagen, smooth muscle cells, and angiogenesis persists  in the aneurysm sac. As thrombus dissolves, aneurysm recurrence may occur unless fibrotic tissue has already filled the spaces between the implanted coils. Polymer coated coils, although intended to increase aneurysm filling density, have not shown efficacy in clinical trials, suggesting a fundamental gap in knowledge regarding the mediators and mechanisms of action of durable aneurysm healing.

Dr. Hosaka’s lab has shown that osteopontin (OPN) sustain-releasing coils produce a robust tissue ingrowth response, and has found that IL-17(A) is transiently expressed in OPN-coiled aneurysms at  day 1 following coil treatment. The proposed anti-IL-17 therapy would intend to mitigate aneurysm recurrence with coiling. They will further investigate the relationship between duration of IL-17 blockade and neutrophil recruitment in the context of OPN-mediated murine aneurysm healing.

Research Objective: The goal of Dr. Hosaka’s proposal is to assess feasibility and potential duration of anti-IL-17 neutralizing antibody as an ancillary treatment in the context of aneurysm coiling, and to gain insight into the aneurysm healing cascade. This will be achieved through evaluating the temporal cascade of IL-17 blockade on neutrophil infiltration in OPN-coiled aneurysm healing, as well as determining the optimal duration of IL-17 blockade treatment for durable aneurysm healing. 

Outcomes: Using this grant from the Aneurysm and AVM Foundation, Dr. Hosaka and his team will work to facilitate the long-term goal of their research to improve treatment for cerebral aneurysms by defining the process of aneurysm healing and employing agents to accelerate and improve that process. This work is directly translatable and deliverable to patients, and future directions after establishing basic mechanisms of aneurysm healing in the mouse model will be to test in a rabbit aneurysm model, the direct precursor to human trials. 

Source: Koji Hosaka, Associate Scientist, University of Florida Division of Sponsored Programs. This research summary has been adapted and edited from Dr. Hosaka's research proposal.