2021 Theses Doctoral

Generating a Mouse Model of Symptomatic and Asymptomatic Intracerebral Hemorrhage by Applying High-Pressure Focused Ultrasound

Collier, Crystal Marie Destiny

Intracerebral hemorrhage defines a category of neurological disease that spans the full range of possible clinical outcomes. At one end of the spectrum is hemorrhagic stroke, an often debilitating neurologic condition with substantial morbidity and mortality while cerebral microhemorrhage at the other end of the spectrum can go completely unnoticed as they are often asymptomatic. Despite the distinct clinical outcomes both conditions share a common risk factor, uncontrolled hypertension. Here we set out to generate a novel mouse model of intracerebral hemorrhage with pressure as the mode of hemorrhage induction.

To conduct our studies, we utilize high pressure focused ultrasound in combination with injected microbubbles to cause hemorrhage. We applied this technique at two different pressures resulting in striatal hemorrhage induction with distinct phenotypic outcomes. Following induction at the higher-pressure, mice show evidence of lateral motor deficit and other signs of impairment. Mice with hemorrhage induced at the lower pressure show no behavioral signs of neurological deficit. We employ immunofluorescence and western blotting to understand the cellular responses to intracerebral hemorrhage in these mice. We find evidence of inflammation and cell death following high-pressure induction of intracerebral hemorrhage. Lower pressure induction of intracerebral hemorrhage lacks signs of cell death but shows apparent inflammation. We have created a novel pressure-dependent mouse model of symptomatic and asymptomatic intracerebral hemorrhage by applying high intensity focused ultrasound in combination with circulating microbubbles.