Thomas P Davis

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The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and the central nervous system (CNS). Although originally observed by Paul Ehrlich in 1885, the nature of the BBB was debated well into the 20th century. The anatomical substrate of the BBB is the cerebral microvascular endothelium, which, together with astrocytes,(More)
Disruption of the tight junctions (TJs) of the blood-brain barrier (BBB) is a hallmark of many CNS pathologies, including stroke, HIV encephalitis, Alzheimer's disease, multiple sclerosis and bacterial meningitis. Furthermore, systemic-derived inflammation has recently been shown to cause BBB tight junctional disruption and increased paracellular(More)
Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJ) that are critical for maintaining brain homeostasis and low permeability. Both integral (claudin-1 and occludin) and membrane-associated zonula occluden-1 and -2 (ZO-1 and ZO-2) proteins combine to form these TJ complexes that are anchored to the(More)
Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, lambda-carrageenan, or complete Freund's adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity(More)
The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study(More)
There is a paucity of therapies for most neurological disorders--from rare lysosomal storage diseases to major public health concerns such as stroke and Alzheimer's disease. Advances in the targeting of drugs to the CNS are essential for the future success of neurotherapeutics; however, the delivery of many potentially therapeutic and diagnostic compounds(More)
P-glycoprotein (Pgp, ABCB1) is a critical efflux transporter at the blood-brain barrier (BBB) where its luminal location and substrate promiscuity limit the brain distribution of numerous therapeutics. Moreover, Pgp is known to confer multi-drug resistance in cancer chemotherapy and brain diseases, such as epilepsy, and is highly regulated by inflammatory(More)
Increased cerebrovascular permeability is an important factor in the development of cerebral edema after stroke, implicating the blood-brain barrier (BBB) in the pathology of stroke. Present investigations modeled stroke at the level of the cerebral capillary endothelium by analyzing BBB permeability changes to the membrane-impermeant marker [14C]sucrose(More)
The blood-brain barrier (BBB) adapts to a variety of pathological processes. Little is known about the effects of nicotine exposure on BBB function and the ability to adapt to stroke conditions. We have demonstrated, using a well-characterized in vitro BBB model, bovine brain microvessel endothelial cells (BBMEC) model, that nicotine and its major(More)
The blood-brain barrier (BBB) is critical to the health of the central nervous system. The BBB is formed primarily by the presence of tight junctions (TJ) between cerebral microvessel endothelial cells. In light of the known effects of nicotine on endothelial cell biology, the specific effects of nicotine on the in vivo BBB were examined. Using in situ(More)