Many therapeutic drugs are excluded from entering the brain, due to their lack of transport through the blood-brain barrier (BBB). To overcome this problem, we have developed a novel method in which short, naturally derived peptides (16-18 amino acids) cross the cellular membranes of the BBB with high efficiency and without compromising its integrity. The antineoplastic agent doxorubicin (dox) ...

Effective pharmacologic treatment of pain with opioids requires that these drugs attain efficacious concentrations in the central nervous system (CNS). A primary determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood-brain barrier (BBB) efflux transporter that is involved in brain-to-blood transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor ...

As P-glycoprotein (Pgp) inhibition at the blood-brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[(11)C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[(11)C]verapamil in whole-brain gray matter incre...

The blood-brain barrier (BBB) is a physical and metabolic barrier that separates the central nervous system from the peripheral circulation. Central nervous system drug delivery across the BBB is challenging, primarily because of the physical restriction of paracellular diffusion between the endothelial cells that comprise the microvessels of the BBB and the activity of efflux transporters that...

Recently neuro-inflammation and cognitive impairment has attracted attention. It has been suggested that obesity lead to cognitive impairments induced by neuro-inflammatory markers like nuclear factor kappa B (NF-kB) and reduced neurotrophin factors like brain-derived neurotrophic factor (BDNF) in the hippocampus. Also, increased blood brain barrier (BBB) permeability. Because of the neuro-prot...

The in vivo restrictive properties of the blood brain barrier (BBB) largely arise from astrocyte and pericyte synergistic cell signaling interactions that underlie microvessel endothelial cells (BMEC). In relevant direct contact between astrocytes, pericytes, BMECS, to our knowledge, has not been established conventional Transwell® based vitro screening models BBB. We hypothesize a design exper...

Furanocoumarin derivatives, known as components of grapefruit juice, showing inhibitory effects against P-glycoprotein (P-gp) in the intestine are also contained in the plants of rutaceae and umbelliferae families, which are used as components of Kampo extract medicines. In this study, we investigated the inhibitory effects of byakangelicol and rivulobirin A, known as furanocoumarins showing P-...

endothelial cells present in brain are unique and differ from other peripheral tissues in a number of ways, which ensures specific brain endothelial barrier properties. endothelial dysfunction is the earliest event in the initiation of vascular damage caused by inflammation. various micrornas (mirna) have been discovered in different cellular components of the blood bran barrier (bbb). mirnas a...