• Journal of Pharmaceutical Investigation
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• v.23 no.1
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• pp.1-9
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• 1993

The endothelial cell of brain capillary called the blood-brain barrier (BBB) has carrier-mediated transport systems for nutrients and drugs. The mechanism of the BBB transport of basic and acidic drugs has been reviewed and examined for endogenous transport systems in BBB in WKY and SHRSP. Acidic drugs such as salicylic acid and basic drugs such as eperisone are taken up in a carrier mediated manner through the BBB via the monocarboxylic acid and amine transport systems. The specific dysfunction for the choline transport at the BBB in SHRSP would affect the function of the brain endothelial cell and brain parenchymal cell. The utilization of the endogenous transport systems of monocarboxylic acid and amine could be promising strategy for the effective drug delivery to the brain.

• Journal of Korean Neurosurgical Society
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• v.50 no.1
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• pp.45-47
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• 2011

Abnormal contrast enhancement on brain computed tomography (CT) scan after diagnostic or interventional angiography is not rare, and has known to be induced by temporary blood-brain barrier (BBB) disruption from contrast media. Furthermore, it has been regarded as clinically subtle, but reported to have no symptom or mild transient symptoms. However, we recently experienced two cases of serious BBB disruption during the acute period after coiling of an unruptured intracranial aneurysm. One patient presented with an unruptured paraclinoid internal carotid artery (ICA) aneurysm on the right and the other with an unruptured right supraclinoid ICA aneurysm. Both patients showed similar findings on immediate postembolization CT scan and clinical courses after coiling. Typical radiological, clinical characteristics of BBB disruption were described. In addition, the role of immediate postembolization CT scan are also discussed.

• Journal of Korean Neurosurgical Society
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• v.48 no.6
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• pp.524-527
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• 2010

Temporary disruption of the blood-brain barrier (BBB) after cerebral angiography is presumably caused by nonionic radiographic contrast medium (CM). We hereby report a case of 58-year-old woman who developed decreased mentality, global aphasia and aggravated right hemiparesis after cerebral angiography. Brain CT examination demonstrated gyriform enhancement throughout the left cerebral cortex and thalamus. MR diffusion did not reveal acute infarction. MR angiography did not show any stenosis, spasm or occlusion at the major cerebral vessels. Follow-up CT scan after 1 day did not show any gyriform enhancement. Worsened neurologic signs and symptoms were improved completely after 7 days. In the present study, disruption of the BBB with contrast medium after angiography seems to be the causative factor of transient neurologic deterioration.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.239-252
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• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.17-23
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• 2022

Boron neutron capture therapy is a precision treatment technology that selectively destroys only tumor cells by irradiating thermal neutrons after accumulating boron drugs in tumor cells. Brain tumor is difficult to diagnose and treat due to the low permeability and targeting of drugs caused by the blood-brain-barrier. Crossing the BBB is essential for drug delivery to the brain. In this study, we designed and synthesized a novel compound incorporating benzothiazole to develop a boron drug with high BBB permeability and selectivity for brain tumor cells. In addition, their potential as a BNCT drugs was evaluated.

• BMB Reports
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• v.49 no.5
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• pp.255-262
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• 2016

The disease known as cerebral cavernous malformations mostly occurs in the central nervous system, and their typical histological presentations are multiple lumen formation and vascular leakage at the brain capillary level, resulting in disruption of the blood-brain barrier. These abnormalities result in severe neurological symptoms such as seizures, focal neurological deficits and hemorrhagic strokes. CCM research has identified 'loss of function' mutations of three ccm genes responsible for the disease and also complex regulation of multiple signaling pathways including the WNT/β-catenin pathway, TGF-β and Notch signaling by the ccm genes. Although CCM research is a relatively new and small scientific field, as CCM research has the potential to regulate systemic blood vessel permeability and angiogenesis including that of the blood-brain barrier, this field is growing rapidly. In this review, I will provide a brief overview of CCM pathogenesis and function of ccm genes based on recent progress in CCM research.

• Biotechnology and Bioprocess Engineering:BBE
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• v.8 no.4
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• pp.246-251
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• 2003

The blood-brain barrier (BBB) is composed of the brain capillaries, which are lined by endothelial cells displaying extremely tight intercellular junctions. Several attempts at creating an in vitro model of the BBB have been met with moderate success as brain capillary endothelial cells lose their barrier properties when isolated in cell culture. This may be due to a lack of recreation of the in vivo endothelial cellular environment in these models, including nearly constant contact with astrocyte foot processes. This work is motivated by the hypothesis that growing endothelial cells on one side of an ultra-thin, highly porous membrane and differentiating astrocyte or astrogliomal cells on the opposite side will lead to a higher degree of interaction between the two cell types and therefore to an improved model. Here we describe our initial efforts towards testing this hypothesis including a procedure for membrane fabrication and methods for culturing endothelial cells on these membranes. We have fabricated a 1 $\mu\textrm{m}$ thick, 2.0 $\mu\textrm{m}$ pore size, and 55% porous membrane with a very narrow pore size distribution from low-stress silicon nitride (SiN) utilizing techniques from the microelectronics industry. We have developed a base, acid, autoclave routine that prepares the membranes for cell culture both by cleaning residual fabrication chemicals from the surface and by increasing the hydrophilicity of the membranes (confirmed by contact angle measurements). Gelatin, fibronectin, and a 50/50 mixture of the two proteins were evaluated as potential basement membrane protein treatments prior to membrane cell seeding. All three treatments support adequate attachment and growth on the membranes compared to the control.

• Science of Emotion and Sensibility
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• v.11 no.4
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• pp.565-574
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• 2008

Functions of human brain including sensibility and emotion may be affected by drugs mediated by the blood-brain barrier (BBB). The present study was performed to evaluate whether injection route, volume and concentration of mannitol could alter the degree of disruption of the BBB. Under urethane anesthesia, female Sprague-Dawley rats were infused with 20% mannitol into the right internal carotid artery (ICA). In the other group, intravenous injection of mannitol through the femoral vein was performed. Evans blue(EB) dye was used as a marker of BBB disruption. When mannitol was injected via the ICA, the content of EB dye in the ipsilateral hemisphere was markedly increased. However, the content of EB in the brain was not increased when mannitol was injected via the femoral vein, even though the volume or concentration of mannitol was increased. These results suggest that the BBB was disrupted only through ICA injection route and this may provide a useful strategy for transient opening of the BBB to control the functions of human brain.

• Journal of Life Science
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• v.33 no.9
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• pp.754-765
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• 2023

Exosomes are a type of extracellular vesicle containing proteins and messenger and microRNAs; they are secreted by all cell types. Once released, exosomes are selectively taken up by other cells adjacent or at a distance, releasing their contents and reprogramming the target cells. Since exosomes are natural vesicles produced by cells as small sizes, it is generally accepted that exosomes have a non-toxic nature and non-immunogenic behaviors. Recently, exosomes have elicited scientific attention as drug delivery vehicles to the central nervous system. The central nervous system has a blood-brain barrier that makes it difficult for drugs to penetrate. Thus, the blood-brain barrier has been a major obstacle to the development of drugs for treating neurodegenerative diseases. However, accumulating evidence suggests that exosomes can cross the blood-brain barrier primarily through transcytosis. Consequently, exosomes are expected to become a new delivery vehicle that can cross the blood-brain barrier and deliver drugs into the brain parenchyma. In addition, since different types of exosomes are secreted depending on the cell type and disease state, exosomes can also be utilized as biomarkers for the diagnosis of diseases in the central nervous system. In this review, we summarized recent research trends on exosomes, including clinical trials as biomarkers and treatment options for diseases in the central nervous system.

• Reproductive and Developmental Biology
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• v.34 no.3
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• pp.153-159
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• 2010

The 34 potently pig pheromonal odorants (1-32, 5755 & 7113) through structure-based virtual screening and ligand-based virtual screening method were selected and their ADMET and pharmacokinetics characters were evaluated and discussed quantitatively. The pheromonal odorants were projected on the following pre-calculated models, Caco-2 cell permeability, blood-brain barrier permeation, hERG inhibition and volume-distribution. From the results of in silico study, it is found that an optimal compound (31) either penetrating or have a little ($P_{caco2}$=-8.143) for Caco-2 cell permeability, moderate penetrating ability ($P_{BBB}$=0.082) for blood-brain barrier permeation, the low QT prolongation ($P_{hERG}$=1.137) for the hERG $K^+$ channel inhibition, and low distribution into tissues ($P_{VD}$=-5.468) for volume-distribution. Therefore, it is predicted that the compound (31) a topical application may be preferable from these based foundings.