• Biomolecules & Therapeutics
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• 제14권1호
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• pp.45-49
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• 2006

The purpose of this study was to clarify the efflux transport system of choline from brain to blood across the blood-brain barrier (BBB) in rats using the brain efflux index (BEI) method. $[^3H]$Choline was micro-injected into parietal cortex area 2 (Par2) of the rat brain, and was eliminated from the brain with elimination halflife of 45 min. The BBB efflux clearance of $[^3H]$choline was about 124 mL/min/g brain, which was determined from combination of an elimination rate constant $(1.54X10^{-2}min^{-1})$ and the distribution volume in the brain (8.05 mL/g brain). The efflux of $[^3H]$choline was inhibited by unlabeled choline in a dose-dependent manner and was significantly inhibited by cationic substrates, such as hemicholinium-3 and tetraethylammonium (TEA). These results suggest that the BBB may act as an efflux pump for choline to reduce the excessive choline concentration in the brain interstitial fluid.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.179-183
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• 2008

In the present study, we examined the effects of several therapeutics of Alzheimer's disease, such as donepezil hydrochloride, tacrine and $\alpha$-phenyl-n-tert-butyl nitrone (PBN) on choline efflux from brain to circulating blood. The brain-to-blood efflux of [$^3H$]choline in rats was significantly inhibited by tacrine and PBN. Also the [$^3H$]choline efflux was reduced by tacrine and donepezil hydrochloride in the TR-BBB cells, in vitro the blood-brain barrier (BBB) model. These results suggest that these drugs may influence choline efflux transport from brain to blood and regulate the choline level in brain resulting in the increase of acetylcholine synthesis.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.441-451
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• 2017

Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both in vivo and in vitro. In vivo study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an in vitro model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both in vivo and in vitro imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or N-methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [$^3H$]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.

• BMB Reports
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• 제55권5호
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• pp.213-219
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• 2022

The blood-brain barrier (BBB) is an interface between cerebral blood and the brain parenchyma. As a gate keeper, BBB regulates passage of nutrients and exogeneous compounds. Owing to this highly selective barrier, many drugs targeting brain diseases are not likely to pass through the BBB. Thus, a large amount of time and cost have been paid for the development of BBB targeted therapeutics. However, many drugs validated in in vitro models and animal models have failed in clinical trials primarily due to the lack of an appropriate BBB model. Human BBB has a unique cellular architecture. Different physiologies between human and animal BBB hinder the prediction of drug responses. Therefore, a more physiologically relevant alternative BBB model needs to be developed. In this review, we summarize major features of human BBB and current BBB models and describe organ-on-chip models for BBB modeling and their applications in neurological complications.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.200.1-200.1
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• 2003

The purpose of this study is to examine whether an brain to blood efflux system for taurine is present on the blood-brain barrier (BBB) or not and this efflux transport system is regulated by CNS cell damage with oxidative stress agent such as diethyl maleate (DEM) or tumor necrosis factor-a (TNF-${\alpha}$), by using the brain efflux index (BEI) method. The brain efflux index value is defined as the relative amount of test compound efflux from cerebrum compared with that of a reference compound, [$\^$14/C] carboxyinulin, which has limited BBB permeability. (omitted)

• 대한방사성의약품학회지
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• 제7권1호
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• pp.3-10
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• 2021

For successful boron neutron caputre therapy, it is essential to develop a boron drug with a selective accumulation capacity for tumors. In particular, in order to apply boron neutron caputre therapy to brain tumors, drugs with good blood-brain barrier penetration are required. In this study, two low-molecular-weight boron compounds were introduced as brain tumor boron neutron caputre therapy drugs, and their physical and biological efficacy were evaluated. Among them, B2 showed good blood-brain barrier permeability and a high brain/blood ratio. From these results, it is expected that B2 can be used as a useful boron drug for boron neutron caputre therapy in brain tumors.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.94-95
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• 2002

Drug targeting to the central nervous system (CNS) is the limiting factor in CNS drug development because most of drug do not cross the brain capillary endothelial wall, which forms the blood-brain barrier (BBB) in vivo. One strategy for drug targeting to the brain is to use endogenous BBB transport systems. (omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.112-112
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• 2002

The age- and gender-related differences in acute toxicity and opening of blood-brain barrier induced by an organophosphate soman were investigated in rats. To assess acute toxicity, young (7 weeks old) and old (12 weeks old) male and female rats were subcutaneously administered with various dose levels of soman.(omitted)

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.112-112
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• 2002

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.90-91
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• 2002

The brain is unique as target for drug delivery because it is an organ with the greatest blood supply, which receives about 20% of the cardiac output in humans and is highly restricted by a tight vascular barrier, the blood-brain barrier (BBB). Since the BBB forms the interface between blood and brain, the biology of the BBB plays a role in multiple disciplines other than pharmacology, physiology, pathology and neurosciences. (omitted)