• 한국음향학회지
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• 제41권5호
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• pp.564-569
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• 2022

인체의 다른 장기들과 달리, 뇌는 혈뇌장벽(Blood-Brain Barrier, BBB)라는 보호 장치가 존재하여 뇌혈관내 물질들이 뇌조직으로 투과되는 것을 제한하는 역할을 한다. 이러한 BBB는 알츠하이머, 뇌종양 등 다양한 뇌질환에 직접적으로 전달이 필요한 약물의 투과까지 제한하기 때문에 치료 효능 검증 및 임상 적용이 어려운 것으로 보고되고 있다. 이러한 문제를 극복하기 위해 비침습적 특성의 집속 초음파(Focused Ultrasound, FUS)를 뇌의 국소 부위에 조사할 경우 마이크로버블의 음향공동화 현상으로 인해 BBB가 일시적으로 개방될 수 있는 기술이 개발되었으며, 해당 기술을 안전성 및 유효성 검증, 약물 전달 효율을 증대시킬 수 있는 다양한 연구가 전 세계적으로 수행되고 있다. 따라서, 본 논문에서는 알츠하이머, 뇌종양 등 뇌질환 치료를 위해 활발히 연구가 진행중인 집속초음파 기반 BBB 개방 기술에 대한 연구 동향을 분석하였다.

• Biomolecules & Therapeutics
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• 제10권4호
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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.

• BMB Reports
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• 제52권2호
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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.

• BMB Reports
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• 제41권5호
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• pp.345-352
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• 2008

The cerebral microvessels possess barrier characteristics which are tightly sealed excluding many toxic substances and protecting neural tissues. The specialized blood-neural barriers as well as the cerebral microvascular barrier are recognized in the retina, inner ear, spinal cord, and cerebrospinal fluid. Microvascular endothelial cells in the brain closely interact with other components such as astrocytes, pericytes, perivascular microglia and neurons to form functional 'neurovascular unit'. Communication between endothelial cells and other surrounding cells enhances the barrier functions, consequently resulting in maintenance and elaboration of proper brain homeostasis. Furthermore, the disruption of the neurovascular unit is closely involved in cerebrovascular disorders. In this review, we focus on the location and function of these various blood-neural barriers, and the importance of the cell-to-cell communication for development and maintenance of the barrier integrity at the neurovascular unit. We also demonstrate the close relation between the alteration of the blood-neural barriers and cerebrovascular disorders.

• Journal of Korean Neurosurgical Society
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• 제66권2호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.69.2-69.2
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• 2003

The purpose of this study is to examine whether the efflux system for taurine from brain to blood is present on the blood-brain barrier (BBB) using the brain efflux index (BEl) method and taurine transport system is regulated by CNS cell damage with oxidative stress agent such as diethyl maleate (DEM) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in vivo. ［$^3$H]Taurine was microinjected into parietal cortex area 2 (Par2) of the rat brain, and was eliminated from the brain with efflux transport rate of 1.22 10$\^$-2//min, and the process is saturable with a $K_{m}$ of 43.5 ${\mu}$M. (omitted)

• BMB Reports
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• 제56권4호
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• pp.240-245
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• 2023

Glial cells play important roles during neurogenesis and in maintaining complex functions of the nervous system. Here, we report the characterization of a gene, Sdr, which contains a putative insulin-like growth factor receptor domain and is required to maintain critical nervous system functions in Drosophila. Sdr is expressed in glial cells during embryonic and larval stages of development, but its role in adult flies is poorly understood. As insulin signaling is important throughout the lifespan in human, we investigated the Sdr's role in adult flies. Our results demonstrate that Sdr is expressed on surface glial cells that surround the nervous system. Mutation of Sdr did not affect development but caused defects in locomotion and lifespan. Sdr mutants also showed increasingly severe defects in the blood-brain- and blood-retina-barriers as they aged. Therefore, we suggest a novel role of Sdr in maintaining the integrity of the blood-brain- and blood-retina-barriers in adult flies.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.107-107
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• 2003

The purpose of this study is to examine that the efflux transport system for choline from brain to blood is present at the blood-brain barrier (BBB) using brain efflux index (BEI) method. ［$^3$H］Choline was microinjected into parietal cortex area 2 (Par2) region of rat brain, and was eliminated from the brain with an apparent elimination half life of 45 min. The BBB efflux clearance of ［$^3$H］choline was 0.12 $m\ell$/min/g brain, which was calculated from the efflux rate constant (1.5${\times}$10$\^$-2/ min$\^$-1/) and the distribution volume in the brain slice (8.1 $m\ell$/g brain). This process was saturable and significantly inhibited by various organic cationic compounds including hemicholinium-3, tetraethylammonium chloride (TEA) and verapamil, by antioxidant, ${\alpha}$-phenyl-n-tert-butyl nitrone (PBN), and by Alzheimer's disease therapeutics, such as acetyl $\ell$-carnitine and tacrine. In conclusion, this finding is the first direct in vivo evidence that choline is transported from brain to the blood across the BBB via a carrier-mediated efflux transport process.

• Archives of Pharmacal Research
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• 제29권4호
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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.