• Journal of Korean Neurosurgical Society
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• v.56 no.5
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• pp.383-389
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• 2014

Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.

• Journal of Life Science
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• v.25 no.11
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• pp.1230-1234
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• 2015

GATA binding protein 6 (GATA6) is a transcription factor that is expressed in the early blastocyst stage and controls the expression of important genes in the differentiation and development of the heart, pancreas, and intestine. This study confirmed the role of GATA6 in cell differentiation and organ development using mouse embryonic stem cells and zebrafish, respectively. First, the mouse embryonic stem cells were differentiated into pacemaker cardiomyocytes. An RT-PCR analysis revealed that the expression of the GATA6 gene was greatly increased from day 4 of differentiation. The expression of GATA6 was upregulated prior to increased expression of NK2 homeobox 5 (Nkx2.5) and myocyte enhancer factor 2C (MEF2C), which are critical transcription factors involved in regulating heart formation. To examine the role of GATA6 in development, GATA6 morpholino was microinjected into zebrafish embryos. Knockdown of GATA6 expression significantly decreased the heart size and heart rate in the zebrafish compared to a control. In addition, the brains were degenerated in the GATA6 morpholino-injected zebrafish. Acridine orange staining showed that knockdown of GATA6 expression increased apoptotic cells in the brain. Interestingly, knockdown of GATA6 expression decreased apoptotic cells in the early bud stage. This study points to the importance of the GATA6 gene in heart and brain development.

• Journal of the Korean Society of Radiology
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• v.10 no.4
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• pp.241-246
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• 2016

The purpose of this study was to investigate the problems of low signal-to-noise ratio(SNR) of single-shot turbo spin echo(SS-TSE) by quantifying numerically decreased signal to noise ratio. Thirty five patients without brain disease underwent diffusion MRI in 3T scanner from July to October in 2015. Single shot echo planar imaging(SS-EPI) which is conventionally used in MRI was taken to compared SS-TSE in SNR of medulla oblongata. As a result, SNR of SS-TSE diffusion(b0=$314.41{\pm}42.96$, b1000=$117.33{\pm}14.04$) is than SS-EPI diffusion(b0=$514.84{\pm}48.97$, b=$208.65{\pm}25.70$) lower in b=0 image(38.9%) and b=1,000 image(43.8%). Thus, diffusion MR using SS-EPI of MS-EPI should be taken for diagnosis of disease in brain stem due to decreased SNR of diffusion using SS-TSE.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.293-303
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• 2023

Background and Objectives: The physiological oxygen tension in fetal brains (~3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1𝛼/Notch regulatory interactions as well as our observations that Hif-1𝛼 and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance. Methods and Results: Here we found that physioxia (3% O₂) compared to normoxia (21% O₂) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions. Conclusions: Notch signalling does not influence the fate decision of midbrain NSCs cultured in vitro in physioxia, where other factors like Hif-1𝛼 might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.

• BMB Reports
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• v.51 no.10
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• pp.481-483
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• 2018

Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.288-293
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• 1995

In the present study, we tested whether lead intoxication could change the thiamine content and the activity of transketolase, one of thiamine-dependent enzymes, in the brain of rats. It was also tested whether administration of excessive thiamine can reverse the toxic manifestation of lead in the lead intoxicated rats. Four groups of Wistar rats were prepared: 1) control group, 2) lead treated group, 3) lead plus thiamine treated group and 4) thiamine deficient group. Each group of animals was divided into three subgroups based on ages: 3, 7 and 16 weeks. Lead concentration, thiamine content and the activity of transketolase in three different brain regions, i.e.,, telencephalon, brain stem and cerebellum, were measured in each group. Lead concentrations in brain regions of the lead treated group were significantly higher than those of the control group, and those of the lead plus thiamine treated group were significantly decreased from those of the lead treated group. Thiamine contents in the brain regions of the lead treated group were significantly lower than those of the control group, and those of the lead plus thiamine treated group were recovered back to those of the control group. Activities of transketolase in the brain regions of the lead treated group and the thiamine deficient group were significantly lower than those of the control group, while those of the lead plus thiamine treated group were higher than the lead treated group. The results from the present study suggest that neurotoxicity following lead intoxication in rats may be mediated, at least in part, through the changes of thiamine status and consequently thiamine-dependent biochemical reactions such as theactivity of transketolase.

• Journal of Korean Neurosurgical Society
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• v.29 no.2
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• pp.217-221
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• 2000

Objective : Brainstem hemorrhages usually result in much higher mortality and morbidty than any other intracranial vascular lesions. The purpose of the study is to evaluate the relationship of the radiological classification of the lesions and the clinical outcomes, and to evaluate the value of such classification on the choice of management modality. Method : Thirty seven patients with primary brainstem hemorrhage were managed medically or surgically between Oct. 1995 and Mar. 1998. The lesions were classified as two groups based on radiological findings as follows : Focal subependymal hematoma(group I, n＝7) and diffuse tegmentobasilar hemorrhage(group II, n＝30). The outcomes at discharge were retrospectively reviewed according to such classification. Result : The most common clinical pictures and radiological findings in each group were as followings : 1) Group I : focal compressive lesion which displaces rather than destroys brain tissue. It occurs in a younger age group and causes neurological deficits which are often partially reversible. Operative hematoma evacuation was performed in 43.3%. Their mean improved Glasgow Coma Scale(GCS) score was 4.7. 2) Group II : hypertensive brain stem hemorrhage. It usually causes a diffuse lesion occurring in an older age group and most often associated with profound irreversible neurological deficits which are often fatal. Operative hematoma evacuation was performed in 16.7%. Their mean improved GCS score was 1.4. In both conservatively treated group I and II has no siginificant clinical improvement. Conclusion : Although there is an overlap among them and the size of the group is small, the pathophysiologic classification of this lesion based on clinical features and radiological findings may be useful for decision of treatment method.

• The Korean Journal of Pain
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• v.31 no.3
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• pp.174-182
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• 2018

Background: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. Methods: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. Results: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). Conclusions: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.

• BMB Reports
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• v.44 no.12
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• pp.793-798
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• 2011

Recently, pluripotency induction or cellular reprogramming by introducing critical transcription factors has been extensively studied, but has been demonstrated only in vitro. Based on reports that Oct4 is critically involved in transforming neural stem cells into pluripotent cells, we used the lentiviral vector to introduce the Oct4 gene into the hippocampal dentate gyrus (DG) of adult mice. We examined whether this manipulation led to cellular or behavioral changes, possibly through processes involving the transformation of NS cells into pluripotent cells. The Oct4 lentivirus-infused group and the green fluorescent protein lentivirus-infused group showed a similar thickness of the DG and a comparable level of synaptophysin expression in the DG. Furthermore, our behavioral analyses did not show any differences between the groups concerning exploratory activity, anxiety, or memory abilities. This first trial for pluripotency induction in vivo, despite negative results, provides implications and information for future studies on in vivo cellular reprogramming.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.327-337
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• 2023

Objectives: Epilepsy is a neurological condition characterized by repeated seizures attributable to synchronous neuronal activity in the brain. The study evaluated the effect of acetone extract of Adansonia digitata stem bark (ASBE) on seizure score, cognition, depression, and neurodegeneration as well as the level of Gamma-Aminobutyrate acid (GABA) and glutamate in Pentylenetetrazol-kindled rats. Methods: Thirty-five rats were assigned into five groups (n = 7). Groups 1-2 received normal saline and 35 mg/kg PTZ every other day. Groups 3-4 received 125 mg/kg and 250 mg/kg ASBE orally while group 5 received 5 mg/kg diazepam daily for twenty-six days. Group 3-5 received PTZ every other day, 30 mins after ASBE and diazepam. Results: The results showed that Pentylenetetrazol (PTZ) induces seizure, reduces mobility time in force swim test and decreases the normal cell number in the brain. It also significantly decreases (p < 0.05) catalase, superoxide dismutase and reduced glutathione activities compared to the ASBE pre-treated rats. Pre-treatment with ASBE reportedly decreases seizure activities significantly (p < 0.05) and increases mobility time in the force swim test. ASBE also significantly elevate (p < 0.05) the normal cell number in the hippocampus, temporal lobe, and dentate gyrus. Conclusion: ASBE reduced seizure activity and prevented depression in PTZ-treated rats. It also prevented neurodegeneration by regulating glutamate and GABA levels in the brain as well as preventing lipid peroxidation.