• Biomedical Science Letters
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• v.11 no.2
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• pp.221-225
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• 2005

To investigate the spectroscopic findings of embolized lesions induced with a fat-emulsion technique with magnetic resonance images (MRI). A fat emulsion was made with 0.1 ml of triolein and 20 ml of normal saline. In 12 cats, the internal carotid artery was infused with the fat emulsion. Contrast-enhanced T1-weighted MRI and multivoxel spectroscopy were obtained at 1 hour, 1 and 4 days, and 1 week after embolization. NAA (N-acetylaspartate), Cr (creatine) and Cho (choline) were evaluated on the spectroscopy. Statitistical analysis wsperformed at the embolized and contralateral normal hemisphere in the integral and amplitude of NAA, Cr and Nho in time course. Also NAA/Cr and Cho/Cr were compared in both hemisphere and in time course. The emboli zed lesions showed contrast enhance ments on Gd-enhanced Tl-weighted i~ages at 1 hour. This contrast enhancement was decreased at day 1, and id not appear agter day 4. In spectroscopy, the embolized hemisphere showed no statistical difference to the normal contralateral side at 1 hour and in time course. NAA/Cr and Cho/Cr were not significantly different in both hemispheres at 1 hour and in time course. Cerebral-fat embolism induced by a triolein emulsion in cats revealed no statistical difference on MR spectroscopy. Triolein-emulsion can be used in the study of blood-brain barrier.

• Annals of Clinical Neurophysiology
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• v.16 no.2
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• pp.55-61
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• 2014

Background: Viruses can cause either meningitis or encephalitis. It is unclear why some people suffer from aseptic meningitis, and others acquire aseptic encephalitis when infected with the same viral pathogens. The aim of this study was to compare demographic and laboratory factors between patients with aseptic meningitis and encephalitis. Methods: The demographic and laboratory differences were analyzed according to age, sex, diabetes, hypertension, C-reactive protein in the blood, white blood cell and protein in the cerebrospinal fluid, and glucose ratio (cerebrospinal fluid/blood). Additionally, we analyzed the nation-wide differencesin age between the patients with aseptic meningitis and those with encephalitis in Korea. Results: The patients with aseptic encephalitis were older, more likely to have hypertension, and had higher levels of C-reactive protein than did the patients with aseptic meningitis. However, the numbers of white blood cells in the cerebrospinal fluid were significantly higher in the patients with meningitis than in the patients with encephalitis. Multivariable analysis revealed that age >49 years, hypertension and a C-reactive protein level >5.81 mg/dL were independent and significant variables in the prediction of aseptic encephalitis. Additionally, the patients with aseptic encephalitis were older than those with aseptic meningitis in the nation-wide Korean database. Conclusions: Older age, hypertension, and higher levels of C-reactive protein are useful factors for the prediction of aseptic encephalitis.

• Journal of Life Science
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• v.30 no.12
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• pp.1118-1127
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• 2020

Alzheimer's disease causes progressive neuronal loss that leads to cognitive disturbances. It is not currently curable, and there is no way to stop its progression. However, since medical treatment for Alzheimer's disease is most effective in the early stages, early detection can provide the best chance for symptom management. Biomarkers for the diagnosis of Alzheimer's disease include amyloid β (Aβ) deposition, pathologic tau, and neurodegeneration. Aβ deposition and phosphorylated tau can be detected by cerebrospinal fluid (CSF) analysis or positron emission tomography (PET). However, CSF sampling is quite invasive, and PET analysis needs specialized and expensive equipment. During the last decades, blood-based biomarker analysis has been studied to develop fast and minimally invasive biomarker analysis method. And one of the remarkable findings is the involvement of platelets as a primary source of Aβ in plasma. Aβ can be transported across the blood - brain barrier, creating an equilibrium of Aβ levels between the brain and blood under normal condition. Interestingly, a number of clinical studies have unequivocally demonstrated that plasma Aβ42/Aβ40 ratios are reduced in mild cognitive impairment and Alzheimer's disease. Together, these recent findings may lead to the development of a fast and minimally invasive early diagnostic approach to Alzheimer's disease. In this review, we summarize recent advances in the biomarkers of Alzheimer's disease, especially the involvement of platelets as a source of peripheral Aβ production and its potential as a blood-based biomarker.

• 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 Ginseng Research
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• v.45 no.2
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• pp.264-272
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• 2021

Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

• Journal of Life Science
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• v.32 no.8
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• pp.611-621
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• 2022

Dimethyl sulfoxide (DMSO) is commonly used as control or vehicle solvent in preclinical research of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) due to its ability to dissolve lipophilic compounds and cross the blood brain barrier. However, the biochemical effects of DMSO on the outcomes of preclinical research are often overlooked. In the present study, we investigated whether the long-term oral administration of 5% DMSO affects the neurological, functional, and histological disease phenotype of the copper/zinc superoxide dismutase glycine 93 to alanine mutation (SOD1-G93A) mouse model of amyotrophic lateral sclerosis. SOD1-G93A transgenic mice showed shortened survival time and reduced motor function. We found that administration with DMSO led to increased mean survival time, reduced neurological scores, and improved motor performance tested using the rotarod and grip strength tests. On the other hand, DMSO treatment did not attenuate motor neuron loss in the spinal cord and denervation of neuromuscular junctions in the skeletal muscle. These results suggest that DMSO administration could improve the quality of life of the SOD1-G93A mouse model of ALS without affecting motor neuron denervation. In conclusion, the use of DMSO as control or vehicle solvent in preclinical research may affect the behavioral outcomes in the SOD1-G93A mouse model. The effect of the vehicle should be thoroughly considered when interpreting therapeutic efficacy of candidate drugs in preclinical research.

• Macromolecular Research
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• v.11 no.3
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• pp.183-188
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• 2003

The controlled delivery of anticancer agents using biodegradable polymeric implant has been developed to solve the problem of penetration of blood brain barrier and severe systemic toxicity. This study was performed to prepare 5-FU-loaded poly (L-lactide-co-glycolide) (PLGA) wafer fabricated microparticles prepared by two different method and to evaluate their release profile for the application of the treatment of brain tumor. 5-FU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC). SEM observation of the 5-FU-loaded PLGA microparticles prepared by rotary solvent evaporation method showed that 5-FU was almost surrounded by PLGA and significant reduction of crystallinity of 5-FU was confirmed by XRD. In case of release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by mechanical mixing, the release profile of 5-FU followed near first order release kinetics. In contrast to the above result, release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by rotary solvent evaporation method followed near zero order release kinetics. These results indicate that preparation method of the 5-FU-loaded PLGA microparticles to fabricate into wafers was contributed to drug release profile.

• Parasites, Hosts and Diseases
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• v.49 no.1
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• pp.1-8
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• 2011

The pathogenesis and pathophysiology of Acanthamoeba infections remain incompletely understood. Phospholipases are known to cleave phospholipids, suggesting their possible involvement in the host cell plasma membrane disruption leading to host cell penetration and lysis. The aims of the present study were to determine phospholipase activities in Acanthamoeba and to determine their roles in the pathogenesis of Acanthamoeba. Using an encephalitis isolate (T1 genotype), a keratitis isolate (T4 genotype), and an environmental isolate (T7 genotype), we demonstrated that Acanthamoeba exhibited phospholipase $A_2$ (PLA$_2$). and phospholipase D (PLD) activities in a spectrophotometry-based assay. Interestingly, the encephalitis isolates of Acanthamoeba exhibited higher phospholipase activities as compared with the keratitis isolates, but the environmental isolates exhibited the highest phospholipase activities. Moreover, Acanthamoeba isolates exhibited higher PLD activities compared with the PLA$_2$. Acanthamoeba exhibited optimal phospholipase activities at $37^{\circ}C$ and at neutral pH indicating their physiological relevance. The functional role of phospholipases was determined by in vitro assays using human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. We observed that a PLD-specific inhibitor, i.e., compound 48/80, partially inhibited Acanthamoeba encephalitis isolate cytotoxicity of the host cells, while PLA$_2$-specific inhibitor, i.e., cytidine 5'-diphosphocholine, had no effect on parasite-mediated HBMEC cytotoxicity. Overall, the T7 exhibited higher phospholipase activities as compared to the T4. In contract, the T7 exhibited minimal binding to, or cytotoxicity of, HBMEC.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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• pp.3671-3675
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• 2012

${\beta}$-Amyloid accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Since early detection of ${\beta}$-amyloid may facilitate more successful and timely therapeutic interventions, many investigators have focused on developing AD diagnostic reagents that can penetrate the blood-brain barrier (BBB). Oleanolic acid (OA) is a substance found in a variety of plants that has been reported to prevent the progression of AD in mice. In this study, we synthesized and evaluated a new radioligand in which OA was conjugated to lactoferrin (Lf, an iron-binding glycoprotein that crosses the BBB) for the diagnosis of AD. In an in vitro study in which OA-Lf was incubated with ${\beta}$-amyloid (1-42) aggregates for 24 h, we found that OA-Lf effectively inhibited ${\beta}$-amyloid aggregation and fibril formation. In vivo studies demonstrated that $^{123}I$-OA-Lf brain uptake was higher than$^{123}I$-Lf uptake. Therefore, radiolabeled OA-Lf may have diagnostic potential for ${\beta}$-amyloid imaging.

• The Korean Journal of Nuclear Medicine
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• v.34 no.5
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• pp.433-435
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• 2000

A 6000-year-old male with carcinoma of the prostate and cerebral infarction underwent a Tc-99m MDP bone scintigraphy for the evaluation of skeletal metastases. Bone scintigraphy (Fig. 1) showed multiple areas of increased uptake of Tc-99m MDP in the skull, spine, and ribs representing skeletal metastases. Two different patterns of uptake occurred in the skull region (Fig. 1A-C); one represents bony metastasis and the ether represents cerebral infarction. The shape, size, location, intensity, and border of the increased uptake differed between the two lesions. An oval-shaped pattern with smaller size, greater intensity and more sharply defined border in the frontal region was consistent with bony metastasis. A rectangular-shaped pattern with larger size, lesser intensity and relatively indistinct border in the temporo-parieto-occipital region was consistent with cerebral infarction. Increased uptake of bone-seeking radiotracers in cerebral infarction has been reported previously.$^{1-4)}$ A suggested mechanism by which bone-seeking radiotracers accumulate in the necrotizing cerebral tissue is an alteration of the blood-brain barrier induced during cerebral infarction, which results in entry of the radiotracers into the extracellular space of the brain.$^{4)}$ Brain CT (Fig. 2) performed 7 days before and one month after the bone scintigraphy revealed lesions on the right temporo-parieto-occipital region consistent with acute hemorrhagic and chronic cerebral infarction, respectively.