Modulating BBB Permeability in Malignant Glioma

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

The permeability of the blood-brain barrier (BBB) in a growing glioma is poorly understood. Independently, perfusion and enhancement of contrast agents have been the standard for measuring an open or closed BBB. With the use of in vitro studies and animal models, we can evaluate in real time, changes in BBB permeability with intratumoral microdialysis and imaging. Aim 1: To characterize the time-dependent dynamic changes of the BBB/BTB during malignant glioma progression Aim 2: To identify and pharmacologically target common signaling pathways involved in glioma stem cell self-renewal and BBB/BTB integrity Aim 3: To determine the penetration of currently used chemotherapeutic agents into malignant gliomas and peritumoral tissue using intracerebral microdialysis Our research aims to identify changes in drug concentrations and tumor dynamics as the invasive glioma progresses. Current studies focus use of vasoactive mediators and G-protein coupled receptor agonists, e.g. Regadenoson, to transiently increase BBB permeability. Additional studies center around disturbing communication of invasive glioma cells with tumor endothelium and supportive cells through barriergenesis pathways (WNT, AKT, etc.). Our clinical studies mainly involve evaluating drug concentration changes within the tumor/tumor microenvironment as a surrogate of BBB integrity and treatment response. The major goal of the DTAP laboratory investigations is to develop novel experimental therapeutics, the most promising of which will hopefully be brought to the clinic to treat adults and children with incurable malignant brain tumors.