The major focus in this laboratory is to elucidate the mechanisms by which leukocytes and pathogens invade the central nervous system (CNS). Movement of cellular elements into the CNS is typically limited by brain microvascular endothelial cells (BMEC) comprising the blood-brain barrier (BBB). It is thus believed that alterations in the BBB contribute to the pathogenesis of various neuroinflammatory, neuroinfectious and neurodegenerative diseases such as multiple sclerosis, AIDS dementia complex and Alzheimer disease. To evaluate how the BBB may be modified in these conditions, we are using both in vitro and in vivo approaches. The in vitro approach involves transwell assays on primary BMECs, isolated and cultured in our lab [Fig. 1]. Such “BBB models” are routinely constructed in the laboratory from mouse or human BMECs, and enable direct measurement of leukocyte transendothelial migration (TEM) and permeability to a wide host of substrates [Fig. 2]. The mechanisms by which cytokines and chemokines influence TEM and permeability at the BBB are currently being investigated with these culture models.