Current interests are focused on the role of blood-brain barrier in the pathogenesis of cerebral small vessel disease and vascular dementia. Pathologic disruption of blood-brain barrier function by both chemical and cellular mediators alters the protected environment of the central nervous system (CNS), resulting in dysfunction and injury in a number of disease conditions. Normal blood-brain barrier function is essential to isolate the CNS from the chemical and immunologic environment of the peripheral vascular system. Physiologic regulation of blood-brain barrier permeability maintains a stable ionic environment in the CNS while permitting the entry of nutrients and precursor molecules and removal of waste materials and metabolites, but blocks the entry of harmful endogenous or exogenous blood-borne agents and severely restricts transmigration of blood leukocytes. The goal of my current work is to characterize substances deposited in brain vessel walls through leakage of plasma components across the endothelial barrier and to study the reactive processes that may be incited by such deposition. Most current work concentrates on the study of human tissue obtained from autopsies, but studies of specific mechanisms in spontaneously hypertensive, stroke prone rats are also planned.
I also have an interest in brain injury in chronic alcoholism, and I participate in collaborative studies on neuropathology of viral encephalitis, neuromuscular disease, cerebrovascular disease, genetic brain disease and toxicology with other investigators in pathology, neurology, medicine, pediatrics, biochemistry and ophthalmology.