scholarly journals Toward Eradicating HIV Reservoirs in the Brain: Inhibiting P-Glycoprotein at the Blood–Brain Barrier with Prodrug Abacavir Dimers

2011 ◽  
Vol 134 (6) ◽  
pp. 2976-2980 ◽  
Author(s):  
Hilda A. Namanja ◽  
Dana Emmert ◽  
David A. Davis ◽  
Christopher Campos ◽  
David S. Miller ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Hiv Reservoirs ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

scholarly journals Nonlinear accumulation in the brain of the new taxoid TXD258 following saturation of P-glycoprotein at the blood-brain barrier in mice and rats

2003 ◽  
Vol 138 (7) ◽  
pp. 1367-1375 ◽  
Author(s):  
Salvatore Cisternino ◽  
Fanchon Bourasset ◽  
Yves Archimbaud ◽  
Dorothée Sémiond ◽  
Gérard Sanderink ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood–brain barrier

2002 ◽  
Vol 38 (6) ◽  
pp. 339-348 ◽  
Author(s):  
Michel Demeule ◽  
Anthony Régina ◽  
Julie Jodoin ◽  
Alain Laplante ◽  
Claude Dagenais ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
Efflux Pump ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Inhibition of P-glycoprotein Activity at the Primate Blood-Brain Barrier Increases the Distribution of Nelfinavir into the Brain but Not into the Cerebrospinal Fluid

2007 ◽  
Vol 35 (9) ◽  
pp. 1459-1462 ◽  
Author(s):  
Amal Kaddoumi ◽  
Sung-Up Choi ◽  
Loren Kinman ◽  
Dale Whittington ◽  
Che-Chung Tsai ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

P2-347: Absence of MDR-1 P-glycoprotein at the blood-brain barrier increased the passage of blood-borne exogenous Aβ peptides across the BBB into the brain

2010 ◽  
Vol 6 ◽  
pp. S415-S416
Author(s):  
Wandong Zhang ◽  
Huaqi Xiong ◽  
Shanshan Shen ◽  
Aimee Jones ◽  
Peilin Huang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Aβ Peptides ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain ◽  
Mdr 1

scholarly journals Functional activity of p-glycoprotein in blood-brain barrier during experimental par-kinson's syndrome

2019 ◽  
Vol 27 (2) ◽  
pp. 150-159
Author(s):  
Ivan V. Chernykh ◽  
Aleksey V. Shchulkin ◽  
Pavel Yu. Mylnikov ◽  
Maria V. Gatsanoga ◽  
Maria M. Gradinar ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Intravenous Administration ◽  
Functional Activity ◽  
Brain Barrier ◽  
Renal Tubules ◽  
Parkinson's Syndrome ◽  
Parkinson’S Syndrome ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Background. P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter with broad substrate specificity that is localized in hepatocytes, enterocytes, epithelial renal tubules, and also in tissue barriers, including blood-brain barrier (BBB). Increased Pgp activity in BBB is one of the reasons for the pharmacoresistance of a number of CNS diseases. Aim. Analysis of Pgp functional activity in BBB during experimental Parkinson's syndrome. Materials and Methods. The work was performed on 90 Wistar rats, divided into 3 series (n=30 in each). The 1 series (control) was subcutaneously injected sunflower oil once a day for 7 days, and Pgp activity in BBB was assessed on the 8th day. The 2 and 3 series (pathology control) - were administered rotenone at a dose of 2.5 mg/kg once a day for 7 and 28 days respectively to simulate parkin-sonism. At the end of the experiment Pgp activity was estimated. To confirm Parkinson's syndrome, in addition to the clinical picture, level of dopamine in midbrain and striatum was determined using enzyme-linked immunosorbent assay. Pgp functional activity in BBB was assessed by the degree of penetration of its marker substrate fexofenadine into the brain after its intravenous administration at a dose of 10 mg/kg. The content of fexofenadine in the blood plasma and in brain tissue was estimated by the area under pharmacokinetic curve of the substance (in the blood or brain tissues) - AUC0-t(plasma) or AUC0-t(brain) respectively. To assess the BBB permeability the ratio AUC0-t(brain) / AUC0-t(plasma) was calculated. Results. Rotenone administration led to the development of parkinsonism typical picture: muscle stiffness, hypokinesia, gait instability. There was a decrease in dopamine level in the striatum after 7 days by 69.6% (p=0.095), after 28 days - by 93.9% (p=0.008), in midbrain - by 72.7% (p=0.095) and 68.7% (p=0.032) respectively. Fexofenadine AUC0-t(plasma) and AUC0-t(brain) after its intravenous administration to control rats were 266.2 (246.4; 285.6) μg/ml*min and 5.9 (5.8;6.6) µg/g*min respectively, AUC0-t(brain) /AUC0-t(plasma) - 0.020 (0.019; 0.022). When rotenone was for 7 days administered - fexofenadine AUC0-t(brain) increased 2.02 times (p=0.0163), AUC0-t(brain) / AUC0-t(plasma) - 2.4 times (p=0.0283). 28 days administration of rotenone led to augmentation of AUC0-t(brain) of fexofenadine by 1.75 times (p=0.0283), AUC0-t(brain) / AUC0-t(plasma) - by 2.27 times (p=0.0163). Conclusions. The development of Parkinson’s syndrome, caused by the administration of rotenone, inhibits Pgp functional activity in BBB, which is confirmed by the accumulation in the brain marker substrate of the transporter - fexofenadine.

scholarly journals Activating PKC-β1 at the blood—brain barrier reverses induction of P-glycoprotein activity by dioxin and restores drug delivery to the CNS

2011 ◽  
Vol 31 (6) ◽  
pp. 1371-1375 ◽  
Author(s):  
Xueqian Wang ◽  
Brian T Hawkins ◽  
David S Miller
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transport Activity ◽  
Aryl Hydrocarbon ◽  
Kinase C ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Glycoprotein Transport ◽  
The Brain

Upregulation of blood-brain barrier (BBB) P-glycoprotein expression causes central nervous system (CNS) pharmacoresistance. However, activation of BBB protein kinase C-β1 (PKC-β1) rapidly reduces basal P-glycoprotein transport activity. We tested whether PKC-β1 activation would reverse CNS drug resistance caused by dioxin acting through aryl hydrocarbon receptor. A selective PKC-β1 agonist abolished the increase in P-glycoprotein activity induced by dioxin in isolated rat brain capillaries and reversed the effect of dioxin on brain uptake of verapamil in dioxin-dosed rats. Thus, targeting BBB PKC-β1 may be an effective strategy to improve drug delivery to the brain, even in drug-resistant individuals.

scholarly journals Impact of P-Glycoprotein Inhibition and Lipopolysaccharide Administration on Blood-Brain Barrier Transport of Colistin in Mice

2010 ◽  
Vol 55 (2) ◽  
pp. 502-507 ◽  
Author(s):  
Liang Jin ◽  
Jian Li ◽  
Roger L. Nation ◽  
Joseph A. Nicolazzo
Keyword(s):  
Blood Brain Barrier ◽  
Systemic Inflammation ◽  
Brain Barrier ◽  
Brain Uptake ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Colistin Sulfate ◽  
The Brain ◽  
Concentration Ratios

ABSTRACTThe aim of this study was to investigate the factors limiting the blood-brain barrier (BBB) transport of colistin in healthy mice and to assess the impact of systemic inflammation on the transport of this antibiotic across the BBB. Colistin sulfate (40 mg/kg) was administered subcutaneously to Swiss outbred mice as single and multiple doses to determine any relationship between brain uptake and plasma concentrations of colistin. To assess the effect of P-glycoprotein (P-gp) on BBB transport, colistin sulfate (5 mg/kg) was concomitantly administered intravenously with PSC833 or GF120918 (10 mg/kg). Systemic inflammation was induced by three intraperitoneal injections of lipopolysaccharide (LPS; 3 mg/kg), and BBB transport of colistin was subsequently measured following subcutaneous administration and by anin situbrain perfusion. The brain uptake of colistin was low following single and multiple subcutaneous doses, with brain-to-plasma concentration ratios ranging between 0.021 and 0.037, and this was not significantly enhanced by coadministration of GF120918 or PSC833 (P> 0.05). LPS significantly increased the brain uptake of subcutaneously administered colistin with area under the brain concentration time curve (AUCbrain) values of 11.7 ± 2.7 μg·h/g and 4.0 ± 0.3 μg·h/g for LPS- and saline-treated mice, respectively (mean ± standard deviation). Similarly,in situperfusion of colistin led to higher antibiotic brain concentrations in LPS-treated animals than in saline-treated animals, with colistin brain-to-perfusate concentration ratios of 0.019 ± 0.001 and 0.014 ± 0.001, respectively. This study demonstrates that the BBB transport of colistin is negligible in healthy mice; however, brain concentrations of colistin can be significantly enhanced during systemic inflammation, as might be observed in infected patients.

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