Assay of Possible Injury Responses to Brain After Application of High-Intensity Focused Ultrasound for Blood-Brain Barrier Disruption
Glioblastoma Mulitforme (GBM) is a malignant brain tumor of the central Nervous System (CNS), which causes death in a patient within just months. It typically had the form of a dense collection of cells (the 'bulk tumor') along with diffuse infiltration of tissue beyond the bulk in the form of isolate tumor cells (ITCs). Typically the bulk tumor can be resected. However, the ITCs remain. Due to their location in the CNS, ITCs are protected by a system known at Blood Brain Barrier (BBB). In the CNS, the BBB plays a protective role by restricting the movement of blood-borne molecules from the blood supply into the brain and spinal cord. This system however, also prevents many pharmacological agents necessary for treatment of GBM into the brain. Disruption of the BBB is vital to increasing efficacy of the treatments.
In our lab, High Intensity Focused Ultrasound (HIFU) has been used for BBB disruption. As described in a paper under review, HIFU applied to a region of interest on the cortex disrupts the BBB, without damage to brain tissue in over half the cases. Moreover, this disruption lasts for up to 72 hours, time enough for several applications of chemotherapeutic agents. It is of interest to know the longer-term evolution of HIFU lesions for the purpose of BBB disruption. Hypothesis: HIFU application to a region of interest disrupts the Blood Brain Barrier without causing structural damage to the brain itself that manifests beyond three days.
This hypothesis will be tested in vivo on 20 Wister Rats. At various points after HIFU application, the subjects will be sacrificed and perfused, and their brains harvested and sent for histological staining for a variety of injury responses in addition to gross morphological changes in neurons and glia. This will give data points for damage after HIFU application well beyond those currently obtained.
