• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.39-47
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• 2010

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.

• Journal of Chest Surgery
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• v.34 no.9
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• pp.653-661
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• 2001

Background: Retrograde cerebral perfusion(RCP) is one of the methods used for brain protection during aortic arch surgery. The author previously published the data, however, for the safety of it, there still remains many controversies. The author performed RCP and checked various parameters to clarify the possibility of early detection of cerebral injury. Material and Method: The author used pigs(Landrace species) weighing 25 to 30kg and performed RCP for 120 minutes. After weaning of cardiopulmonary bypass, we observed pigs for another 120 minutes. Rectal temperature, jugular venous oxygen saturation, central venous pressure were continuously monitored, and the hemodynamic values, histological changes, and serum levels of neuron-specific enolose(NSE) and S100$\beta$ protein were checked. Central venous pressure during RCP was maintained in the range of 20 to 25 mmHg. Result: Flow rates(ml/min) during RCP were 224.3$\pm$87.5(20min), 227.1$\pm$111.0(40min), 221.4$\pm$119.5(60min), 230.0$\pm$136.5(80min), 234.3$\pm$146.1(100min), and 184.3$\pm$50.5(120min). Serum levels of NSE did not increase after retrograde cerebral perfusion. Serum levels of S100$\beta$ protein(ng/ml) were 0.12$\pm$0.07(induction of anesthesia), 0.12$\pm$0.07(soon after CPB), 0.19$\pm$0.12(20min after CPB), 0.25$\pm$0.06(RCP 20min), 0.29$\pm$0.08(RCP 40min), 0.41$\pm$0.05(60min), 0.49$\pm$0.03(RCP 80min), 0.51$\pm$0.10(RCP 100min), 0.46$\pm$0.11(RCP 120min), 0.52$\pm$0.15(CPBoff 60min), 0.62$\pm$0.15(60min after rewarming), 0.76$\pm$0.17(CPBoff 30min), 0.81$\pm$0.20(CPBoff 60min), 0.84$\pm$0.23(CPBoff 90min) and 0.94$\pm$0.33(CPBoff 120min). The levels of S100$\beta$ after RCP were significantly higher than thosebefore RCP(p<0.05). The author could observe the mitochondrial swellings using transmission electron microscopy in neocortex, basal ganglia and hippocampus(CA1 region). Conclusion: The author observed the increase of serum S100$\beta$ after 120 minutes of RCP. The correlation between its level and brain injury is still unclear. The results should be reevaluated with longterm survival model also considering the confounding factors like cardiopulmonary bypass.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.392-409
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• 1998

The present experiment was designed to examine the effects of Jeongjihwan on carecholamines, serotonin, amino acids, lipid peroxide, free radical scavenging activity, malondialdehyde and superoxide dismutase activity in senile brain. It was performed by administering Jeongjihwan extracts of a variety of concentration to senile rats to experimentally determine effects of Jeongjihwan on biochemical changes in senile brain and examine protective effects against neurotoxin. To examine survival rate, the rat's spinal cord sensory ganglion cell pretreated in Jeongjihwan extracts was cultured in oxygen free radical. The results were summarized as follows: 1. Jeongjihwan significantly increased noradrenaline in the hippocampus and hypothalamus of the brain tissue of senile rats, and even though Jeongjihwan increased noradrenaline also in other brain tissue, there was no significance. 2. Jeongjihwan had no effects on dopamine changes in all brain tissue of senile rats. 3. Jeongjihwan significantly increased serotonin, but decreased in other brain tissue. 4. Jeongjihwan increased amino acid in the brain tissue of senile rats. 5. Jeongjihwan significantly decreased lipid peroxide and free radical in the brain tissue of senile rats. 6. Jeongjihwan significantly increased survival rate of nerve cell exposed to oxygen free radical. According to the above results, Jeongjihwan is assumed to improve brain function by reacting on biochemical changes of the senile brain and carries effects of protecting against neurocytotoxicity, and that Jeongjihwan can be used to treat regressive brain disease carrying symptoms of psychoactive disorders.

• Animal cells and systems
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• v.1 no.3
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• pp.467-473
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• 1997

Taurine (2-aminoethanesulfonic acid), one of bioactive amino acid in the mammalian brain, is known to exert inhibitory effects on neurons via GABA receptor. In the present study, we examined effects of taurine on glutamateinduced neurotoxicity on hippocampal neuron cell culture using cell counting method and lactate dehydrogenase (LDH) assay. After 10 d of culture, cells were stimulated with appropriate drugs. Only 43% of cultured neuronal cells survived at one day after stimulation with 500 uM L-glutamate for 10 min. Survival rate was enhanced by 82% in the presence of 10 mM taurine. LDH activity from the culture supernatant incubated with a combination of L-glutamate and taurine was less than half of that with L-glutamate alone. In the next series of experiments, interleukin-6 (IL-6) mRNA expression in cultured astrocytes was investigated using reverse tanscription-PCR (RT-PCR). IL-6 mRNA was detected in the astrocytes stimulated with L-glutamate in a dose-dependent manner, while not detected in the unstimulated control astrocytes. The expression of IL-6 mRNA caused by 10 mM glutamate was inhibited by taurine, but not by GABA. These findings demonstrated a neuroprotective action of taurine against glutamate-induced toxicity.

• BMB Reports
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• v.49 no.2
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• pp.69-70
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• 2016

Mutations of orthodentricle homeobox 2 (OTX2) in human and mice often cause retinal dystrophy and nyctalopia, suggesting a role of OTX2 in mature retina, in addition to its functions in the development of the eye and retina. In support of this, the number of bipolar cells in Otx2^+/− post-natal mouse retina was found to be significantly lower than normal. Degeneration of the cells becomes greater as the mice age, leading to the loss of vision. Especially, the type-2 OFF-cone bipolar cells, which do not express Otx2 mRNA but carry Otx2 protein, are most sensitive to Otx2 haplodeficiency. Interestingly, this bipolar cell subpopulation imports Otx2 protein from photoreceptors to protect itself from glutamate excitotoxicity in the dark. Moreover, in the bipolar cells, the exogenous Otx2 relocates to the mitochondria to support mitochondrial ATP synthesis. This novel mitochondrial activity of exogenous Otx2 highlights the therapeutic potential of Otx2 protein transduction in retinal dystrophy.

• Applied Microscopy
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• v.48 no.1
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• pp.11-16
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• 2018

For Odontamblyopus lacepedii with small and turbid eyes, the gross structure and histology of the olfactory organ, which is important for its survival and protection of the receptor neuron in estuarial environment and its ecological habit, was investigated using a stereo, light and scanning electron microscopes. Externally, the paired olfactory organs with two nostrils are located identically on each side of the snout. These nostrils are positioned at the anterior tip of the upper lip (anterior nostril) and just below eyes covered with the epidermis (posterior nostril). Internally, this is built of an elongated olfactory chamber and two accessory nasal sacs. In histology, the olfactory chamber is elliptical in shape, and lined by the sensory epithelium and the non-sensory epithelium. The sensory epithelium of a pseudostratified layer consists of olfactory receptor neurons, supporting cells, basal cells and lymphatic cells. The non-sensory epithelium of a stratified layer has swollen stratified epithelial cells and mucous cells with acidic and neutral sulfomucin. From these results, we confirmed the olfactory organ of O. lacepedii is adapted to its ecological habit as well as its habitat with burrows at the muddy field with standing and murky waters.

• Journal of Oriental Neuropsychiatry
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• v.10 no.2
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• pp.29-45
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• 1999

As the average life span has been lengthened and the rate of senile population has been raised, chronic degenerative diseases incident to aging have been increased rapidly and become a social problem. With this social background, recently, oxygen radicals(OR) have toxic effects on Central Nervous System and Peripheral Nervous System and cause neuropathy such as Parkinson's Disease, Alzheimer Disease. The purpose of this study is to examine the toxic effects caused by Xanthine Oxidase(XO) and the effects of herbal extracts such as Jokihaeatang(JHT) on the treatment of the toxic effects. For this purpose, experiments with the cultured cell from the cerebrums of new born mice were done. The results of these experiments were as follows. 1. X0, an oxygen radical, decreased the survival rate of the cultured cells on NR assay, MTT assay and amount of neurofilaments and increased the amount of lipid peroxidation. 2. JHT have efficacy of increasing the amount of neurofilaments.

• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.219-226
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• 1998

Cytosine arabinoside(AraC) inhibits DNA synthesis and ${\beta}$-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

• Journal of Life Science
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• v.18 no.3
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• pp.311-317
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• 2008

Pathophysiological oxidative stress results in neuronal cell death mainly due to the generation reactive oxygen species (ROS). In low oxygen situation such as hypoxia and ischemia, excessive ROS is generated. Coptidis Rhizoma (CR) is a traditional medicine used for the incipient stroke. In this report we show that CR water extracts $(1\;{\mu}g/ml)$ exhibited protective effects of neuronal cell death in a hypoxic model (2% $O_2/5%\;CO_2,\;37^{\circ}C,$ 3 hr) of cultured rat cortical cells. We further show that CR water extracts significantly reduced the intensity of green fluorescence after staining with $H_2DCF-DA$ on one hour and three days after hypoxic shock and in normoxia as well. Our results indicate that CR water extracts prevent neuronal death by suppressing ROS generation.

• International Journal of Oral Biology
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• v.42 no.1
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• pp.9-15
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• 2017

Microglia have multiple functions in regulating homeostasis of the central nervous system. Microglia cells have been implicated as active contributors to neuron damage in neurodegenerative disorders. In this study, medicinal plant extracts (MPEs) were used to evaluate the cell-death induction effect in microglia BV-2 cells. Among 35 MPEs tested in this study, 4 MPEs showed less than a 30% cell survival after 24 hours of incubation. These were Foeniculi Fructus, Forsythiae Fructus, Zingiberis Rhizoma and Hedera Rhombea. The concentration showed that 50% cell death ($IC_{50}$) occurred with 33, 83, 67 Ed highlight: Please confirm wording, and $81{\mu}/ml$, respectively. For further study, we chose Zingiberis Rhizoma (ZR) which showed a reasonably low $IC_{50}$ value and an induction of cell death in a relatively narrow range. Western blot analysis showed that ZR-treated cells showed activation of caspase-3 and cleavage of PARP Ed highlight: When an acronym is first presented it needs to be spelled out in both dose- and time-dependent manners. However, the level of Bcl-2 and Bax were not changed by ZR-treatment in BV-2 cells. These results suggest that ZR-induced apoptosis in BV-2 cells occured through caspase-3 activation. The results also suggested that ZR may be useful in developing treatments for neurodegenerative diseases.