• Journal of Korean Neurosurgical Society
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• 제50권1호
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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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• 제48권6호
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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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• 제28권3호
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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.

• 대한방사성의약품학회지
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• 제8권1호
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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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• 제49권5호
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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.

• 감성과학
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• 제11권4호
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• pp.565-574
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• 2008

감성을 비롯한 인간의 뇌 기능은 혈-뇌 장벽을 매개로 약물의 작용에 의해 직접적인 영향을 받을 수 있다. 이 연구는 mannitol의 투여경로와 양, 농도에 의한 혈-뇌 장벽(blood-brain barrier, BBB)의 변화를 알아보고자 수행되었다. 실험동물로서 흰쥐에 20%의 mannitol을 오른쪽 뇌경동맥(internal carotid artery, ICA)을 통하여 주입하였고, 다른 그룹에서는 femoral vein을 통하여 주입하였다. 또한 각기 다른 경로를 이용하여 Evans blue(EB) 염색 시료를 투여한 후 BBB의 변성 정도를 확인하였다. 실험결과 ICA를 통해서 mannitol이 주입된 동물은 동측(ipsilateral side)이 대측(contralateral side)에 비해 EB 염색시료에 의해 영향을 많이 받았으나, femoral vein을 통해서 주입한 경우에는 mannitol의 양과 농도를 증가시켜도 EB 염색시료에 의한 영향이 거의 나타나지 않았다. 이러한 결과는 비록 EB 염색시료의 주입이 ICA를 통해서 또는 정맥경로를 따라서 이루어지더라도, BBB의 변성은 ICA를 통해서 이루어진다고 볼 수 있으며, 이러한 결과는 BBB의 제한적인 조절작용을 통해 인간의 뇌 기능을 이해하는데 좋은 방법을 제공할 수 있다는 것을 시사한다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제8권4호
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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.

• 생명과학회지
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• 제33권9호
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• pp.754-765
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• 2023

엑소좀은 단백질, mRNA 및 miRNA를 포함하고 모든 유형의 세포에서 분비되는 세포 외 소포의 일종이다. 방출된 엑소좀은 인접하거나 멀리 있는 다른 세포에 의해 선택적으로 흡수되어 그 내용물을 방출하고 표적 세포를 재프로그래밍한다. 엑소좀은 세포에 의해 생성되는 작은 천연 소포이므로 무독성과 비면역원성의 특징이 있는 것으로 받아들여지고 있다. 최근에는 엑소좀이 중추신경계에 대한 약물 전달체로 과학적 관심을 받고 있다. 중추신경계에는 약물의 침투를 어렵게 하는 혈뇌장벽이 있고 이는 퇴행성신경질환의 치료제 개발에 큰 걸림돌이 되어왔다. 그러나 축적된 연구결과들을 볼 때, 엑소좀이 주로 트랜스사이토시스를 통해 혈뇌장벽을 통과할 수 있음이 제시되었다. 이러한 결과를 종합하면, 엑소좀은 혈뇌장벽을 넘어 뇌 실질조직에 약물을 전달할 수 있는 새로운 전달 수단이 될 것으로 기대된다. 또한 세포의 종류와 질병상태에 따라 분비되는 엑소좀의 종류가 다르기 때문에 엑소좀은 중추신경계 질환의 진단을 위한 바이오마커로도 활용될 수 있다. 본 총설 논문에서는 중추신경계 질환에 대한 바이오마커 및 치료 옵션으로서의 임상시험을 포함한 엑소좀에 대한 최근 연구동향을 정리하였다.

• Reproductive and Developmental Biology
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• 제34권3호
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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.

• 동의생리병리학회지
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• 제23권4호
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• pp.866-871
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• 2009

Brain edema is a major importance in the pathophysiology of CNS injuries including stroke. Ischemic brain edema results from both cytotoxic edema, which is severe in astrocytes at early stage, and vasogenic edema caused by excessive blood-brain barrier (BBB) permeability. The present study was performed to determine the effect of Rhei Rhizoma on brain edema induced by middle cerebral artery occlusion (MCAO) in the rats. The neurological symptom, total infarct volume and edema index caused by MCAO were measured. The changes of Matrix Metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS) immunoreactivities were also observed. We found that Rhei Rhizoma extract improved the neurological symptom and attenuated the total infarct volume and brain edema caused by ischemic insult. Rhei Rhizoma extract also attenuated the expression of MMP-9 and iNOS. This results suggest that Rhei Rhizoma has a protective effect on the brain edema caused by ischemic insult.