• Journal of Oriental Neuropsychiatry
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• v.18 no.2
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• pp.101-132
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• 2007

Objective : This research investigates the effect of the NogYongDaeBoTang,(NYDBT) on Alzheimer's disease. Method : The effects of the NYDBT extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) acetylcholinesterase(AChE), amyloid precursor proteins(APP), and glial fibrillary acidic protein(GFAP) mRNA the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, and $TNF-{\alpha}$ mRNA; (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer‘s diseased mice induced with ${\beta}A$ were investigated. Results : 1. The NYDBT extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The NYDBT extract suppressed the expression of $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the NYDBT extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by $A{\beta}$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The NYDBT extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, and CD68/CD11b, in the mice with Alzheimer's disease induced by $A{\beta}$. 5. The NYDBT extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by $A{\beta}$. 6. The NYDBT extract reduced the Tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by $A{\beta}$. Conclusions : These results suggest that the NYDBT extract may be effective for the prevention and treatment of Alzheimer's disease.

• Journal of Pharmacopuncture
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• v.14 no.3
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• pp.5-17
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• 2011

Objectives : Gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by middle cerebral artery occlusion is involved with up-regulation of CD81 and GFAP (Glial fibrillary acidic protein). The current study is to examine the effect of the Angelica gigas Nakai(intravenous injection. 100 mg/kg twice in a day) on CD81 and GFAP of the rat in the brain after middle cerebral artery occlusion. Methods : Cerebral infarction was induced by middle cerebral artery occlusion. And after intravenous injection of water extract of Angelica gigas Nakai, the size of cerebral infarction was measured. Examination of optical microscope were also used to detect the expression of CD81 and GFAP in the brain of the rat. Results : The following results were obtained : We found that size of cerebral infarcion induced by MCAO (Middle Cerebral Artery Occlusion) in rats were decreased after intravenous injection of Angelica gigas Nakai. We injected the extract of Angelica gigas Nakai to the MCAO in rats, and the optical microscope study showed that Angelica gigas Nakai had effect on protecting the cells of hippocampus. We found that GFAP, CD81 and ERK of the brain in rats with cerebral infarction after MCAO were meaningfully decreased after intravenous injecting Angelica gigas Nakai. We found that c-Fos expression of the brain in rats with cerebral infarction after MCAO were significantly increased after intravenous injecting Angelica gigas Nakai. Conclusions : These results indicate that Angelica gigas Nakai could suppress the reactive gliosis, which disturbs the astrocyte regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. And the effect may be modulated by the up-regulation of c-Fos and ERK.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.256-264
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• 2022

Ischemic stroke is caused by an occlusion by a thrombus or embolus in a cerebral artery, preventing oxygenated blood from reaching the brain and causing the necrosis of nerve cells. This paper summarizes the serum candidate markers associated with cardiovascular disease and atrial fibrillation (AF) disease that enable an early diagnosis of ischemic stroke studied thus far and compares the odds ratio (OR) of each marker. This study examined the effect size of these serum candidate markers using meta-analysis techniques. The academic database search screening for articles containing the keywords "cardiovascular disease," "atrial fibrillation," "ischemic stroke," and "serum marker" was limited to results for patients with ischemic stroke. The most derived markers in this study were N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), D-dimer, C-reactive protein (CRP), and glial fibrillary acidic protein (GFAP), the rest being investigated individually. In conclusion, NT-pro-BNP appears to be very useful for the early diagnosis of ischemic stroke. Primarily, it is a marker of AF, and more AF markers will be uncovered and studied in the future.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1309-1315
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• 2000

Objectives : We performed an in vivo experiment to investigate the effect of $^{166}Holmium$ and $^{166}Holmium$-chitosan complex($^{166}Ho$-CHICO) on the normal brain of rats and to determine the sublethal dose of $^{166}Ho$-CHICO. Materials and Methods : $^{166}Ho$ is a beta and gamma ray emitter. $^{166}Ho$-CHICO is a novel radio-pharmaceutical complex with chitosan to facilitate the transport of $^{166}Ho$ obtained from Korea Atomic Energy Research Center(Taejon, Korea). It is in acidic form and becomes gel state at alkaline pH. One hundred and seventy consecutive rats were divided into four groups : $^{166}Ho$ treated(n＝50), $^{166}Ho$-CHICO treated(n＝57), saline treated(n＝5) and chitosan treated(n＝5) groups. $^{166}Ho$ and $^{166}Ho$-CHICO were injected into the rat brain stereotactically with various doses of 0.1mCi/$20{\mu}l$, 0.2mCi/$20{\mu}l$, 0.3mCi/$20{\mu}l$, and 0.4mCi/$20{\mu}l$ using an automated microinjector. Nuclear imaging, histopathological and hematological studies were performed in 10 rats in each group at 1 day, 3days, 7 days, 1 month and 3 months after the injections. Results : An infiltration of inflammatory cells and necrotic changes were noted in $^{166}Ho$ treated group at 1 week after the injection. A wedge-shaped tissue defect due to necrosis, lined with infiltrated glial cells in $^{166}Ho$ treated group and a cystic defect lined with reactive astroglial cells in $^{166}Holmium$-CHICO treated group at 3 months after the injection were observed. $^{166}Ho$ alone without chitosan leaked out and caused necrotic lesion on the cerebral surface but $^{166}Holmium$-CHICO treated group did not show this feature. As the dose of $^{166}Ho$ increased, the mortality rates were also increased. The mortality rate of the $^{166}Holmium$-CHICO group was higher than the $^{166}Ho$ treated group at a dose of 0.4mCi/$20{\mu}l$/300g. There was no detectable radioactivity due to the leakage or extravasation from the injected site of the brain on the scintigraphy performed at 1 hour, 24 hours and 48 hours after the injection. There was also no detectable activity of $^{166}Holmium$-CHICO in other organs including spleen, liver and kidney. Conclusions : $^{166}Ho$-CHICO did not leak out to the critical cortical surface of the brain from the injection site and induced radiation changes of the parenchyma around the injection site without cortical damage. The sublethal dose of $^{166}Ho$-CHICO for the normal brain in rats was determined to be 0.2mCi/$20{\mu}l$/300g.

• Journal of Life Science
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• v.25 no.1
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• pp.101-112
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• 2015

A type of cell junction that is formed between different parts within the same cell is called autotypic cell junction. Autotypic junction proteins form tight junctions found between membrane lamellae of a cell, especially in myelinating glial cells. Some of them have postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains, which interact with the carboxyl (C)-terminal PDZ-binding motif of other proteins. PDZ domains are protein-protein interaction modules that play a role in protein complex assembly. The PDZ domain, which is widespread in bacteria, plants, yeast, metazoans, and Drosophila, allows the assembly of large multi-protein complexes. The multi-protein complexes act in intracellular signal transduction, protein targeting, and membrane polarization. The identified PDZ domain-containing proteins located at autotypic junctions include zonula occludens-1 (ZO-1), ZO-2, pals-1-associated tight junction protein (PATJ), multi-PDZ domain proteins (MUPPs), membrane-associated guanylate kinase inverted 2 (MAGI2), and protease-activated receptor (PAR)-3. PAR-3 interacts with atypical protein kinase C and PAR-6, forming a ternary complex, which plays an important role in the regulation of cell polarity. MAGI2 interacts with ${\alpha}$-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptor at excitatory synapses. PATJ is detected in paranodal loops associated with claudin-1. On the other hand, MUPP1 is found in mesaxons and Schmidt-Lanterman incisures with claudin-5. ZO-1, ZO-2, and PAR-3 are found at all three sites. Different distributions of PDZ domain-containing proteins affect the development of autotypic junctions. In this review, we will describe PDZ domain-containing proteins at autotypic tight junctions in myelinating Schwann cells and their roles.

• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.263-271
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• 2001

Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.882-890
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• 2007

Purpose : Preterm very low birth weight infant have high rate of adverse neurodevelopmental sequale. Recently, there have been lots of reports that human umbilical cord blood transplantation ameliorates functional deficits in animal models as hypoxic ischemic injury. This pilot study was undertaken to determine the clinical efficacy and safety of autologous umbilical cord blood cell transplantation for preventing neurodevelopmental sequale in perterm VLBW. Methods : Subjects were 26 preterm infants whose birth weight are less than 1,500 g and delivered under the intrauterine period 34 weeks. Autologous umbilical mononuclear cells (about $5.87{\times}10^7/kg$) were injected to neonate via the umbilical vein on the postnatal 24-48 hour. The therapeutic efficacy was assessed by numbers of nucleated RBC, urinary uric acid/creatinine ratio, concentration of neuron specific enolase (NSE), interleukin 6 (IL6), interleukin-$1{\beta}$ ($IL-1{\beta}$), and glial cell derived neurotrophic factor (GDNF) in serum and cerebrospinal fluid on day 1 and 7. Results : There were no significant differences in the numbers of the nucleated RBC, urinary uric acid/creatinine ratio, concentration of creatine kinase between the transplanted infants and controls. But the nucleated RBC is more likely to be rapidly discharged in the transplanted group. In the transplanted group, the concentrations of IL6, $IL-1{\beta}$, and GDNF were no significant difference between day 1 and 7, although GDNF seemed to be elevated. Serum NSE concentration was significantly elevated after transplantation, but not in CSF. Conclusion : It is suggested that autologous umbilical cord blood transplantation in preterm very low birth weight infant is safe to apply clinical practice. Long term follow up study should be needed to evaluate the potential therapeutic effect of umbilical cord blood transplantation for neuroprotection.

• Applied Microscopy
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• v.35 no.3
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• pp.165-176
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• 2005

Studies on molecular plasticity of Bermann glia (BG) after harmaline-induced Purkinje cell (PC) degeneration in the rat cerebellum. The intimate structural relationship between BG and PC, evidenced by the sheathing of the PC dendrites by veil-like process from the BG has been suggestive of the close functional relationship between these two cell types. However, little is known about metabolic couplings between these cells. This study designed to investigate molecular plasticity of BG in the rat cerebellum in which PCs were chemically ablated by harmaline treatment. Immunohistochemical examination reveals that harmaline induced PC degeneration causes a marked glial reaction in the cerebellum with activated BG and microglia aligned in parasagittal stripes within the vermis. In these strips, activated BG were associated with upregulaion of metallotheionein, while GLAST and was down regulated, as compared with nearby intact area where both BG are in contact with PCs. The data from this study demonstrate that BG can change their phenotypic expression when BG loose their contact with PCs. It is conceivable that activated BG may upregulate structural proteins, metallothionein expression to use for their proliferation and hypertrophy; metallothionein expression to cope with oxidative stress induced by PC degeneration and microglial activation. On the contrary, BG may down regulated expression of GLAST because sustained loss of contact with PCs would eliminate the necessity for the cellular machinery involved glutamate metabolism. In conclusion, BG might respond man to death of PCs by undergoing a change in metabolic state. It seems possible that signaling molecules released from PCs regulates the phenotype expression of BG. Also ultrastructures in the organelles of normal PC and BG are distinguished by mitochondrial appearance, and distributed vesicles at the synaptic area in the cytoplasm.