• The Korea Journal of Herbology
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• v.26 no.4
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• pp.169-180
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• 2011

Objectives : This study aimed at evaluation of the effects of Rhodiola rosea on brain edema and expressions of matrix metalloproteinases (MMPs) related to blood-brain barrier (BBB) disruption. Methods : Brain edema following intracerebral hemorrhage (ICH) was induced by the stereotaxic intrastriatal injection of bacterial collagenase type VII in rats (Sprague-Dawley). Then ethanol extract of Rhodiola rosea was treated once a day for 3 days. Brain edema % and water contents, and BBB leakage were examined. Immunohistochemistry was processed for MMP-9, MMP-12, and iNOS expressions in the brain sections and each immuno-labeled cells were analyzed with image analysis software. Results : 1. Ethanol extract of Rhodiola rosea reduced brain edema following ICH in rats significantly. 2. Ethanol extract of Rhodiola rosea reduced excessive brain tissue water contents following ICH in rats significantly. 3. Ethanol extract of Rhodiola rosea reduced BBB leakage in the cerebral cortex following ICH in rats. 4. Ethanol extract of Rhodiola rosea reduced cellular edema of neurons in peri-hematoma and the cerebral cortex following ICH in rats significantly. 5. Ethanol extract of Rhodiola rosea reduced MMP-9 positive cells in the cerebral cortex following ICH in rats significantly. 6. Ethanol extract of Rhodiola rosea reduced MMP-12 positive vessels in the cerebral cortex following ICH in rats significantly. 7. Ethanol extract of Rhodiola rosea reduced iNOS positive cells in the cerebral cortex and external capsule following ICH in rats significantly. Conclusions : These results suggest that Rhodiola rosea reveals protective effect against brain edema and cytotoxic edema of neurons by means of down-regulation of MMPs and iNOS expressions, and inhibition of BBB leakage.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.17 no.8
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• pp.1947-1954
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• 2013

Previous works for detecting arrhythmia have mostly used nonlinear method such as artificial neural network, fuzzy theory, support vector machine to increase classification accuracy. Most methods require accurate detection of P-QRS-T point, higher computational cost and larger processing time. But it is difficult to detect the P and T wave signal because of person's individual difference. Therefore it is necessary to design efficient algorithm that classifies different arrhythmia in realtime and decreases computational cost by extrating minimal feature. In this paper, we propose arrhythmia detection based on binary coding using QRS feature varibility. For this purpose, we detected R wave, RR interval, QRS width from noise-free ECG signal through the preprocessing method. Also, we classified arrhythmia in realtime by converting threshold variability of feature to binary code. PVC, PAC, Normal, BBB, Paced beat classification is evaluated by using 39 record of MIT-BIH arrhythmia database. The achieved scores indicate the average of 97.18%, 94.14%, 99.83%, 92.77%, 97.48% in PVC, PAC, Normal, BBB, Paced beat classification.

• Biomedical Science Letters
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• v.12 no.2
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• pp.127-130
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• 2006

It is important to coordinated interaction among neurons, astrocytes and endothelial cells to maintain the function of brain. To study their regulatory mechanisms in vitro system, the co-culture system among the isolated cells from brain may be needed. However, the method for purifying brain microvascular endothelial cells (BMEC) far culture have not established yet. In this study, the proper culture methods of mice cells using two different strains, CD1 and C57BL6, to obtain the pure and plentiful endothelial cells were described. The flatted-round forms of CD1 endothelial cells grew on the collagen-IV coating plates, while the purified cells from C57 mice preferred type collagen-I dishes for their growth. Both cells displayed anti-PECAM-1 (CD31) and von Willebrand Factor immune-reactivity. These results indicated that different coating materials not only improve attachment of isolated cells but also promoting growth of cells, suggesting that this method of purifying murine Brain microvascular endothelial cells (BMEC) provides a suitable model to investigate blood-brain-barrier (BBB) properties within neurovascular unit in vitro.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.345-345
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• 1994

BBB opening 에 의란 수용성 약물 및 지용성 약물의 뇌혈관 투과 패턴을 알아보기 위해 모델약물로서 수용성 약물인 $^{99}$Tc-DTPA, 지용성 약물인 Pherlytoin을 선택하여 뇌혈관 투과성(PA)의 증가율을 검토하고자 하였다. 랫트의 좌측 외경동맥(left external carotid artery)에 혈류의 역방향으로 PE-50 catheter를 분지점에서 1-2mm 전까지 삽입하고, 1.6 molal L-(+)-arabinosg 고장액 (1580 mOsm)을 0. 12ml/sec의 일정한 속도로 30초간 infusion 한 후. $^{99}$Tc-DTPA 혹은 phenytoin 약물 용액을 대뢰정맥으로 주사하고, 대뢰동맥으로부터 약물 투여전 및 투여후 10, 30초, 1, 1.5, 2, 3. 4, 5. 7, 10분 간격으르 혈액을 채취하였으며. 마지막 채혈후 즉시 단두하여 뇌조직을 취하였다. 채취한 뇌를 좌, 우반구 및 각 부위별로 분리하고 감마 카운터와 HPLC를 이용하여 뇌증농도를 정량하였다. 또한 뇌 실질 조직내 약물량을 구하기 위해 뇌 혈관내에 존재하는 약물양을 보정하였는데, 이때 계산에 필요한 뇌증 혈액부피의 측정은 $^{99}$Tc-albumin을 이용하여 구하였다.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.391-395
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• 2000

To establish the usefulness of oxytocin (OT) as an analgesic for women in delivery, the pharmacokinetic parameters and blood-brain barrier (BBB) permeability of [$^3H$] OT were obtained using an intravenous injection technique or the internal carotid artery perfusion/capillary depletion (ICAP/CDM) method. Brain uptake of OT was similar to that of sucrose, plasma space marker, indicating that OT has a poor BBB permeability. Moreover, the analgesic effects of OT injected through the jugular vein on nociception were evaluated by the tail-flick method. The antinociceptive effects of OT injected at a dose of 0.2 ${m}g/kg$or 2 ${m}g/kg$ were dose-dependent. In addition, the analgesic effects of OT on the CNS were unaffected by naloxone, a m-receptor antagonist. In a similar manner to the opioid system, OT may play a modulatory role in antinociception.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.112-117
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• 2007

Imaging distribution of ${\beta}-amyloid$ plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the ${\beta}-amyloid$ plaques includes using radiolabeled peptides which can be only applied for peripheral ${\beta}-amyloid$ plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging ${\beta}-amyloid$ plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for ${\beta}-amyloid$ imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for ${\beta}-amyloid$ imaging agent.

• 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.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.53-58
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• 1997

$[Lys^7$]dermorphin, abbreviated K7DA, which has structural features similar to a metabolically stable $\mu$-opioid peptide agonist $[D-Arg^2, Lys^4$]dermorphin analogue (DALDA), but is intrinsically more potent with respect to binding to the $\mu$-opioid peptide receptor. The present studies report on attempts to enhance brain uptake of systemically administered K7DA by conjugation to a complex of streptavidin (SA) and the OX26 murine monoclonal antibody to the rat transferrin receptor, which undergoes receptor-mediated transcytosis through the blood-brain barrier (BBB). SA-OX26 conjugate mediates BBB transport of biotinylated therapeutics. The K7DA is monobiotinylated at the $\varepsilon$-amino group of the $[Lys^7$] residue with cleavable linker using NHS-SS-biotin. The brain uptake of $^{125}I$ labeled biotinylated K7DA ($^{125}I$-bio-SSa-K7DA) was very small and rapidly metabolized after intravenous injection. The brain uptake, expressed as percent of injected dose delivered per gram of brain, of the $^{125}I$-bio-55-K7DA bound to the SA-OX26 conjugate $^{125}I$-bio-SS-K7DA/SA-OX26) was 0.14$\pm$0.01, a level that is 2-fold greater than the brain uptake of morphine. The cleavability of the disulfide linker in vivo in rat plasma and brain was assessed with gel filtration HPLC and intravenous injection of labeled opioid chimeric peptides. The disulfide linker is stable in plasma in vivo but is cleaved in rat brain in vivo. In conclusion, these studies show that delivery of these potential opioid peptides to the brain may be improved by coupling them to vector-mediated BBB drug delivery system.

• Journal of Life Science
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• v.19 no.10
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• pp.1489-1494
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• 2009

This study was designed to investigate the effects of swimming and minocycline on motor function recovery and Bcl-2 expression after spinal cord injury (SCI) in rats. After operation, neurological motor behavior test (BBB scale) on days 1, 4, 7, 10, and 14 were tested. Western blot and immunohistochemical assessment (Bcl-2) were performed on day 14. BBB scale started to show a statistically significant difference on day 7 (p<0.05). On day 14, it showed the most significant (p<0.05) difference. Expression of Bcl-2 increased in all the experimental groups. In particular, the highest expression of Bcl-2 appeared in the swimming and minocycline groups. Based on these results, minocycline and swimming were the most effective factors in the motor behavior function and immunohistochemical assessment of SCI rats.

• The Korea Journal of Herbology
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• v.27 no.2
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• pp.61-67
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• 2012

Objective : Angelica Gigas Nakai is a popular oriental medicine used for the treatment of vascular diseases. The aim of this study is to investigate neuroprotective effect of the water extract of Anelicae Gigantis Radix Palva (AG) in transient middle cerebral artery occlusion (tMCAO)-induced ischemic rats via the regulation of angiogenesis-related molecules. Methods : Sprague-Dawley rats were intraperitoneally administrated with AG water extract at doses of 10, 25, 50 mg/kg body weight after tMCAO (90 min occlusion). reperfusion for 24 hr infarction volumes were measured by 2,3,5-tetrazolium chloride (TTC) staining. Brain tissues were observed neuronal cell injuries by nissl staining, and also brain-blood barrier (BBB) permeability change by evans blue. Expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Tie-2 receptor protein in brain tissues was determined by western blot. Results : AG water extract significantly reduced infarction volume in ischemic brains of rats, degradation of neuronal cell, BBB permeability and expression of VEGF protein dose-dependently. Ang-1 protein was increased dose-dependantly, not significantly. Conclusion : This study suggests that AG water extract shows neuroprotective effect by preventing BBB breakdown, with regulating angiogenesis factor VEGF and Ang-1.