• BMB Reports
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• v.55 no.5
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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.

• Journal of Korean Neurosurgical Society
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• v.66 no.2
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• pp.172-182
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• 2023

Objective : The blood-brain barrier (BBB) is an obstacle for molecules to pass through from blood to the brain. Focused ultrasound is a new method which temporarily opens the BBB, which makes pharmaceutical delivery or removal of neurodegenerative proteins possible. This study was demonstrated to review our BBB opening procedure with magnetic resonance guided images and find specific patterns in the BBB opening. Methods : In this study, we reviewed the procedures and results of two clinical studies on BBB opening using focused ultrasound regarding its safety and clinical efficacy. Magnetic resonance images were also reviewed to discover any specific findings. Results : Two clinical trials showed clinical benefits. All clinical trials demonstrated safe BBB opening, with no specific side effects. Magnetic resonance imaging showed temporary T1 contrast enhancement in the sonication area, verifying the BBB opening. Several low-signal intensity spots were observed in the T2 susceptibility-weighted angiography images, which were also reversible and temporary. Although these spots can be considered as microbleeding, evidence suggests these are not ordinary microbleeding but an indicator for adequate BBB opening. Conclusion : Magnetic resonance images proved safe and efficient BBB opening in humans, using focused ultrasound.

• 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.

• BMB Reports
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• v.52 no.2
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• pp.111-112
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• 2019

Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

• The Journal of the Acoustical Society of Korea
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• v.41 no.5
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• pp.564-569
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• 2022

Blood-Brain Barrier (BBB) is the brain protecting system blocking the inflow of harmful substances into brain parenchyma from brain blood vessel. However, the BBB has a negative effect on the treatment of various brain diseases such as Alzheimer's dementia or brain tumors because it also prevents drug delivery into brain parenchyma. To overcome this problem, a brain drug delivery technique using Focused Ultrasound (FUS) which allows BBB to be temporarily opened by inducing the acoustic cavitation effect of microbubbles has been developed. Thus far, various studies using the FUS technique has been conducted to improve drug delivery efficiency, and therefore, this paper discusses recently developed drug delivery technologies using the FUS-induced BBB opening.

• Biomolecules & Therapeutics
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• v.14 no.1
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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.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.265-275
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• 2006

In the developing brain, capillaries are differentiated and matured into the blood-brain barrier (BBB), which is composed of cerebral endothelial cells, astrocyte end-feet, and pericytes. Since the BBB regulates the homeostasis of central nervous system (CNS), the maintenance of the BBB is important for CNS function. The disruption of the BBB may result in many brain disorders including brain tumors. However, the molecular mechanism of BBB formation and maintenance is poorly understood. Here, we summarize recent advances in the role of oxygen tension and growth factors on BBB development and maintenance, and in BBB dysfunction related with brain tumors.

• Biomolecules & Therapeutics
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• v.16 no.3
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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.

• Proceedings of the PSK Conference
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• 2002.10a
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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)

• Proceedings of the PSK Conference
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• 2002.10a
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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)