Aaron J. Johnson, Ph.D.

My laboratory is interested in neuroimmunology.

Disruption of the Blood Brain Barrier (BBB) is a common pathologic feature of numerous neurological diseases as diverse as glioblastoma, multiple sclerosis, acute hemorrhagic leukoencephalitis (AHLE), epilepsy, HIV dementia, stroke, cerebral malaria and viral hemorrhagic fevers.

Despite the enormous burden of morbidity and mortality due to these neurological diseases associated with CNS vascular permeability, the underlying molecular mechanisms of how inflammatory cells promote BBB disruption remain poorly understood.

My laboratory has developed a novel murine model of CNS vascular permeability that provides a tractable approach to defining specific inflammatory mediators that disrupt the BBB in vivo using Theiler's virus infection. This murine model of BBB disruption is initiated by CNS infiltrating CD8 T cells. Perforin is critical for both CNS vascular permeability and preservation of BBB tight junctions.

The expression of vascular endothelial growth factor (VEGF) and mouse genetic background is critical. Using this model, a major goal of our projects is to test our underlying hypothesis that CD8 T cells utilize perforin to initiate the disruption of cerebral endothelial cell BBB tight junctions. Also addressed in this model system is the cellular source of VEGF in CNS vascular permeability and the identification of inflammatory factors that contribute to BBB disruption.

Defining inflammatory factors that contribute to opening of the blood brain barrier also has application in the delivery of chemotherapeutic agents to the CNS.