Research Study:AcuteBrainInjuryandPlatelet–LeukocyteInteractionsinSubarachnoidHemorrhage
Primary Investigator: Jennifer Frontera, MD, FNCS (Associate Professor of Medicine (Neurology) Cleveland Clinic Lerner College of Medicine and Case Western Reserve University)
Co-Investigators: Thomas M. McIntyre, PhD (Staff Cellular & Molecular Medicine Professor, Molecular Medicine, Cleveland Clinic), Jose Javier Provencio, MD (Assistant Professor of Medicine, Staff Neurointensivist, Cleveland Clinic), Amy S. Nowacki, PhD (Assistant Staff Biostatistician, Cleveland Clinic)
Background: Subarachnoid hemorrhage (SAH) is one of the most devastating forms of stroke. Currently, the most important predictor of how a patient will function after SAH is the early brain injury that occurs at the time of rupture, yet little is known about just how that happens and no therapeutic treatments for acute brain injury are currently available. Dr. Frontera and her team found that platelets become activated after SAH and form aggregates with leukocytes (or small obstructions), which may lead to ischemia acutely after aneurysm rupture. This sequence of events may be responsible, in part, for early brain injury.
Research Objective: The central hypothesis of this project is that platelet activation occurs immediately in SAH, leading to the formation of platelet-leukocyte aggregates, obstruction of the microcirculation, and consequent acute brain injury; and inhibition of platelet activation will lesson this pathogenic process.
The objective of this project is to determine if SAH patients will have higher markers of platelet activation and platelet-leukocyte aggregates compared to controls,and that poor grade SAH patients will have higher markers compared to SAH patients with better admission neurological exams or controls. The expectation is then that platelet-leukocyte aggregates will be weakened by aspirin use.
Outcomes: If it is found that activation of platelets and platelet-leukocyte aggregation are associated with worse early neurological status (implying acute brain injury) and worse long term neurological function after SAH, this would suggest that therapeutic interventions that weaken platelet activation and platelet-leukocyte aggregation might be clinically useful. Identifying the mechanism of acute brain injury after SAH is essential to targeting novel therapeutic interventions. Physicians will be able to both suggest therapies to intervene and lessen a patient’s likelihood of additional stroke as well as better predict the outcome for a patient after SAH.
