• Journal of the Korean Society of Radiology
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• v.81 no.3
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• pp.488-500
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• 2020

Accumulating evidence suggests that Alzheimer's disease (AD) is not only caused by accumulation of abnormal proteins, including amyloid and tau, but is also closely associated with abnormalities in the microvascular environment including the blood-brain barrier (BBB), both of which lead to neuroinflammation and neurodegeneration. Application of in vivo magnetic resonance imaging (MRI) has recently increased to assess BBB permeability in AD and related diseases. Here, we provide a narrative review of BBB permeability-related pathology in Alzheimer dementia and recent MRI research on BBB permeability changes in AD and related diseases. Furthermore, we briefly introduce the measurement of BBB permeability using MRI and its methodological issues.

• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.218-223
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• 2002

This study compared the blood-brain barrier permeability of [$^3H$] taurine in senescence-accelerated mouse (SAM) and normal mouse with common carotid artery perfusion (CCAP) method and intravenous injection technique to establish a possible relation between aging and changes in tissue levels of taurine. The SAM strains show senescence acceleration and age-associated pathological phenotypes similar to geriatric disorders seen in humans. In the result of this experiments, the plasma clearance of [$^3H$]taurine in SAM was almost comparable with that of normal mice by intravenous injection technique, but the brain volume of distribution ($V_{D brain}$) of [$^3H$]taurine in SAM by CCAP method reduced by 85% compared with that in normal mice. These results suggest that aging may have an effect on the brain transport activity of taurine in disease state model animal.

• YAKHAK HOEJI
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• v.46 no.2
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• pp.124-128
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• 2002

The nitrone-based free radical trapping reagent, $\alpha$-phenyl-n-tert-butyl nitrone (PBN) has been proposed as therapeutic agent for stroke. We used this for model drug of development of new drug for neuroprotection. The purpose of this study was to evaluate the blood-brain barrier (BBB) permeability of PBN in Sprague-Dawly (SD) rats. The BBB transport of PBN was investigated in SD rats using internal carotid artery perfusion (ICAP) method at a rate of 4 mι/min for 15 second. We also obtained pharmacokinetic parameters of PBN using single intravenous injection technique. When we estimated BBB permeability of PBN with ICAP method, the brain volume of distribution of PBN was 60.0 $\pm$ 12.0 $\mu\textrm{g}$/ι. The brain uptake of PBN after IV injection at 120 min was 0.15 $\pm$ 0.01%ID/g. The PBN was transported to the brain through the BBB well in rats, because PBN is small molecule (MW 177) and lipid-soluble (log P 1.23) compound.

• Proceedings of the PSK Conference
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• 2003.04a
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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)

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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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.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.165-172
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• 1999

In the present work , the transport mechanism of a capsaicin derivative, DA-5018, through blood-brain barrier (BBB) has been investigated to evaluate the feasibility of potential drug development. The result of pharmacokinetic parameters obtained from the intravenous injection of plasma volume marker,$[3^H]RSA$ and $[{14}^C]DA-5018$, indicated that both AUC, area under the plasma concentration curve and VD, volume of distribution in brain of $[3^H]RSA$ agreed with those reported ($1620{\pm}10 $percentage injected dose minute per milliliter (%IDmin/ml) and $12.0{\pm}0.1{\mu}l/g$, respectively). Elimination half-life and AUC of $[{14}^C]DA-5018$is corrected by the PHLC analysis, 19.6$\pm$1.2 min and 7.69$\pm$0.85% IDmin/ml, respectively. The metabolic rate of $[{14}^C]DA-5018$was very rapid. The blood-brain barrier permeability surface area (PS) product of $[{14}^C]DA-5018$ was calculated to be 0.24$\pm$0.05 $\mu$l/min/g. The result of internal carotid artery perfusion and capillary depletion suggested that [14C]DA-5018 pass through BBB with the time increasingly. Investigation of transport mechanism of $[{14}^C]DA-5018$ using agonist and antagonist suggested that vanilloid (capsaicin) receptor did not exist in the BBB, and nutrient carrier system in the BBB has no effect on the transport of DA-5018. In conclusion, despite the fact that penetration of DA-5018 through BBB is significant, the intact drug found in the brain tissue is small because of a rapid metabolism. Therefore, for the central analgesic effect of DA-5018, the method to increase the metabolic stability in plasma and the brain permeability should be considered.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.192-192
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• 1998

The blood - brain barrier (BBB) expresses high concentrations of transferrin receptor, and it was revealed that anti-transferrin receptor mouse monoclonal antibody (OX26) undergoes transcytosis through the BBB. This property allows the OX26 to serve as a brain drug delivery vector. In an attempt to produce broadly useful targeting agents, genetic engineering and expression techniques have been used to produce antibody-avidin (AV) fusion protein (OX26 IgG3C$\_$H/3-AV). In the present study we estimated the BBB permeability and stability of genetically engineered vector.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.325-332
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• 2016

Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. The blood-brain barrier (BBB), formed by specialized brain endothelial cells that are interconnected by tight junctions, strictly regulates paracellular permeability to maintain an optimal extracellular environment for brain homeostasis. The aim of this study was to elucidate the effects of resveratrol and the role of AMPK in BBB dysfunction induced by lipopolysaccharide (LPS). Exposure of human brain microvascular endothelial cells (HBMECs) to LPS ($1{\mu}g/ml$) for 4 to 24 hours week dramatically increased the permeability of the BBB in parallel with lowered expression levels of occluding and claudin-5, which are essential to maintain tight junctions in HBMECs. In addition, LPS significantly increased the reactive oxygen species (ROS) productions. All effects induced by LPS in HBVMCs were reversed by adenoviral overexpression of superoxide dismutase, inhibition of NAD(P) H oxidase by apocynin or gain-function of AMPK by adenoviral overexpression of constitutively active mutant (AMPK-CA) or by resveratrol. Finally, upregulation of AMPK by either AMPK-CA or resveratrol abolished the levels of LPS-enhanced NAD(P)H oxidase subunits protein expressions. We conclude that AMPK activation by resveratrol improves the integrity of the BBB disrupted by LPS through suppressing the induction of NAD(P)H oxidase-derived ROS in HBMECs.

• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.99-105
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• 2000

This study compared the permeability of $[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ through the blood-brain barrier (BBB) in mice and rats with common carotid artery perfusion (CCAP) method that modified internal carotid artery perfusion (ICAP) method. External carotid artery (ECA) was cannulated with coagulating pterygopalatine artery (PPA) in ICAP method, while CCA was cannulated without coagulating PPA in CCAP method. Also, for evaluation of BBB permeability of drugs in mice and rats, we used intravenous injection technique. The results of CCAP method in mice at a perfusion flow-rate of 2 ml/min, the brian volume of distribution $(V_D)$ of $[^{14}C]sucrose,\;[^3H]taurine,\;[^3H]phenylalanine,\;and\;[^3H]oxytocin$ were similar to the result of ICAP method in rats at perfusion flow rate of 4 ml/min. The area under the plasma concentration-time curve and brain uptake of $[^3H]taurine$ by intravenous injection technique, were $65.5{\pm}9.7%ID^*min/ml\;and\;0.515{\pm}0.093%ID/g$, respectively, in mice, and the corresponding values were $8.00{\pm}0.03%ID^*min/ml\;and\;0.052{\pm}0.003%ID/g$ in rats. But the BBB permeability surface-area product of $[^3H]taurine$ was similar between mice and rats. In conclusion, the CCAP method in mice was simple, fast and comparable to ICAP method in rats for drug permeability through the BBB.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.193-194
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• 1998

Recently, evaluation of brain transport of taurine which is possible to effect on Alzheimer's disease has investigated in rats. Also, internal carotid artery perfusion (ICAP) method is very useful for measuring of blood-brain barrier (BBB) permeability in rats. But ICAP has difficulties to evaluate of BBB permeability in mice especially. In the present study examines neuropharmaceutials permeability through the BBB in mice by common carotid artery perfusion (CCAP) method that modify ICAP method and require simple surgery. The external carotid artery (ECA) is cannulated with coagulating pterygopalatine artery (PPA) on ICAP method, while CCA is cannulated without coagulating PPA on CCAP method. The CCAP method require 4-5 fold higher infusion rate than ICAP method because an additional factor of 2 must be incorporated to adjust for fluid loss to the extracerebral circulation.