• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.167-179
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• 1994

Recent evidence indicates that glial cells have a wide range of funtions which are critical for maintaining a balanced homeostatic environment in the central nervous system(CNS) peripheral nervous system(PNS). Morever, astrocytes are known to participate in the tissue repair and neuroimmunologic events within the CNS through many kinds of growth factors and cytokines. We investigated the effect of $TGF\;{\beta}_1$, on the growth and biochemical changes of rat glial cells in culture. The proliferative effect was determined by $^3H-thymidine$ uptake and the double immunostain with anti-cell-specific marker and anti-Bromodeoxyuridine(BrdU) antibody. To check the effect of biochemical changes we compared the amounts of glial fibrillar acidic protein(GFAP) and the activity of glutamine synthetase(GS) in astrocyte. And the amounts of myelin basic protein and the activity of 2',3'-cyclic nucleotide phosphohydrolase(CNPase) were measured in oligodendrocyte and the amounts of peripheral myelin in Schwann cell. When $TGF\;{\beta}_1$, was treated for 2 days with cultured glial cell, $TGF\;{\beta}_1$, decreased the $^3H-thymidine$ uptake and proliferation index of double immunostain of astrocytes, which indicates the inhibition of astroglial DNA synthesis, but stimulated the growth of Schwann cell. Also, $TGF\;{\beta}_1$, decrease the GS activity and increased the amounts of GFAP in astrocyte. In the case of Schwann cells the amounts of peripheral myelin was increased when treated with $TGF\;{\beta}_1$. However, $TGF\;{\beta}_1$, didn't show any effect on the proliferation and biochemical changes in oligodendrocyte. These results suggest that $TGF\;{\beta}_1$, might have a critical action in the regulation of proliferation and biochemical changes in glial cells, especially astrocyte.

• The Journal of Internal Korean Medicine
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• v.23 no.2
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• pp.191-201
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• 2002

Objectives : This study was designed to investigate the effects of Yukmijihwang-tang on contusion of the mice induced with medicine. Methods : I observed the effects of light and electron microscopes. and examined hematological changes and VEGF-immunohistochemistry. Results : Hematology: Leukocytes were increased significantly in a control group of mice compared with the experimental group. Light microscope : A few neurons were condensed in the 7-day experimental group, but condensed remarkedly in the 3-day control group. Most glial cells were observed in the 3-day experimental group. Edema and dilatation of vessels occurred significantly in the 3-day control group, and these results occurred weakly in the 7-day experimental group. VEGF-immunohistochemistry : VEGF-immunohistochemical reactivity for the glial cells was the highest in the 3-day experimental group, and immunoreactivity for the vessels and neurons highly increased in the 7-day experimental group. Electron microscope : In the 3-day control group, protoplasmic astrocytes concerned with angiogenesis contained weakly developed rough endoplasmic reticulum. and a few of glial filaments were observed. In the 7-day experimental group, the bundles of glial filaments were found in the cytoplasmic process of astrocytes. Conclusion : medication using Yukmijihwang-tang of mice contused by medical stress is highly effective in inflamatory response, curing cell damage and angiogenesis.

• The Journal of Internal Korean Medicine
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• v.21 no.2
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• pp.235-241
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• 2000

호도(胡桃)(Juglandis semen)가 치매에 미치는 영향을 알아보기 위하여 치매(Alzheimer's disease) 유발물질로 알려진 amyloid-{$\beta}(A{\beta})$ 25-35를 흰쥐의 뇌 신경세포의 일종인 astrocyte에 처리한 후 뇌의 신경세포에 대한 독성 및 세포막에서의 지질 과산화에 미치는 영향을 검토하였다. 호도(胡桃)는 $A{\beta})$ 25-35로 인한 신경세포의 파괴를 억제하는 것으로 나타나 신경세포의 손상을 예방하고 보호하는 효과가 있었다. 그리고, 지질의 과산화 지표인 malondialdehyde 생성은 $A{\beta})$ 25-35 처리로 크게 증가하였으나, 호도(胡桃)의 전처리와 후처리로 크게 감소되어 호도(胡桃)가 세포막 파괴로 인한 뇌세포의 손상을 방지하는 것으로 나타났다. 이러한 결과들을 볼 때, 호도(胡桃)는 신경세포의 하나인 astrocyte에 대한 보호효과와 세포막에서 지질의 과산화를 저해 및 $A{\beta})$ 25-35 처리와 같은 치매 유발 독성에 대한 적응능력 향상을 통하여 뇌 신경세포를 보호하는 효과가 있음을 보여주는 것으로 노인성 치매 등의 임상적 응용에 그 효과가 기대된다.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.375-387
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• 2009

Objective : Gyehyuldeung (GHD) has been widely used in oriental medicine for the treatments of cardiovascular and neurological disorders. Thus, its potential facilitatory activity on axonal regeneration was investigated in the rats. Methods: Sprague-Dawley rats were given crush injury at the sciatic nerve and the changes of axon growth after nerve injury on each nerve injury model were investigated with anti-NF-200 antibody, DiI, GAP-43 protein and Cdc2 protein Results : GHD-mediated enhancement of axonal regeneration after crush injury was measured in both qualitative and quantitative ways by immunofluorescence staining with anti-NF-200 antibody and retrograde tracing of fluorescence dye DiI. GAP-43 protein levels were elevated by GHD treatments in the distal injured sciatic nerve and DRG sensory neurons. The neurite outgrowth of DRG sensory neurons was facilitated by GHD treatment when co-cultured with Schwann cells and astrocytes prepared from injured sciatic nerves and injured spinal cord tissues, respectively. It was observed that Cdc2 protein was up-regulated in co-cultured Schwann cells or astrocytes and Cdc2 protein signals were co-localized to a certain extent with those of phospho-vimentin protein. Conclusions : These results suggest that GHD may play a facilitatory role in axonal regeneration by acting on the injured axons and adjacent non-neuronal cells. The current findings may be useful for the development of therapeutic targets through more specific explorations on molecular interactions between herbal components and endogenous factors.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.37-41
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• 2008

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.48-55
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• 2010

Neural progenitor cells (NPCs) differentiate into astrocytes, neurons and oligodendrocytes, which is controlled by various factors in brain. Recent evidences suggest that small molecules modulating the proliferation and differentiation of NPCs may have therapeutic value as well as the potential use as chemical probes. Phylligenin is a lignan with anti-inflammatory activity that is isolated from the fruits of Forsythia koreana. We investigated effects of phylligenin on proliferation and differentiation of NPCs. Treatment of phylligenin decreased the number of proliferating NPCs in culture without effects on the differentiation and survival of neural cells such as neurons and astrocytes. To examine the mechanism of the decreased NPCs number, we performed cell cycle analysis. Proliferation of NPCs was decreased via G1-S transition block by phylligenin treatment, and it was mediated by the increase of p21 level. However, phylligenin did not induce apoptosis of NPCs as determined by TUNEL assay and PARP cleavage. We also found that viability of glioma cell lines such as C6 and U87MG glioma cells, but not that of primary neuron and astrocyte, was inhibited by phylligenin. These results suggest that phylligenin selectively inhibits proliferation of rapidly growing cells such as neural stem cells and glioma cells. Given that the possible role of brain tumor stem cells in the pathology of brain cancers, the inhibitory effects of phylligenin might be useful in the development of new therapeutic agents against brain cancers.

• Journal of Oriental Neuropsychiatry
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• v.20 no.2
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• pp.1-17
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• 2009

Objectives : Alzheimer's disease(AD) is the most common form of dementia, which is characterized by progressive deterioration of memory and higher cortical functions that ultimately results in total degradation of intellectual and mental activities. Nokyongdaebo-tang(Lurongdabutang) has been usually used for the treatment for the deficiency syndrome dementia and amnesia. This experiment was designed to investigate the effect of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on pathological AD model. Methods : The effects of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on cultured spinal cord cells induced by ${\beta}$-amyloid were investigated. The effects of the Nokyongdaebo-tan(Lurongdabutang) hot water extract on the memory deficit mice induced by scopolamine were investigated. Results : 1. ${\beta}$-amyloid treatment on cultured spinal cord cells increased both GFAP-staining intensity of astrocytes and caspase 3 immunoreactivity on cultured cells. Then, Nokyongdaebo-tang(Lurongdabutang) treatment reduced the labeling intensity for both GFAP and caspase 3 proteins in culture cells. 2. Scopolamine treatment into mice increased levels of GFAP-positive astrocytes and caspase 3-labeled cells of the hippocampal subfields dentate hilar region, CA3 and CA1 area. In vivo administration of Nokyongdaebo-tang(Lurongdabutang) attenuated labeling intensity for those two proteins in the same hippocampal areas. Similar effects were observed by the treatment of galanthamine, an inhibitor of acetylcholinesterase. Conclusions : This experiment shows that the Nokyongdaebo-tang(Lurongdabutang) may play a protective role in damaged neural tissues. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. Nokyongdaebo-tang(Lurongdabutang) might be effective for the prevention and treatment of AD.

• Korean Journal of Veterinary Research
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• v.33 no.3
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• pp.465-469
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• 1993

This paper dealt with the histopathological findings on the natural cysticercosis in pigs. Three cases of porcine cysticercosis, which had been kept in the Department of Veterinary Medicine, Cheju. University more than ten years, were histopathologically examined in order to see the host reaction to the parasite. Capsules containing scolex were mainly found in the fascia of skeletal muscle, heart, and brains. Microscopically, cysticerci in the epicardium and the fascia of skeletal muscles were encapsulated with fibroblasts and collagen fibers. Around capsules, there was infiltration of eosinophils, lymphocytes and macrophages, although the degree and severity of inflammatory reaction varied case by case. Cerebral cortex also had the inflammatory exudate of lymphoid cells in the vicinity of the scolex. whereas perivascular lymphocytic cuffings were commonly seen around capsules. GFAP immunoreactive fibers formed a limiting membrane along the outer side of capsules. There was also proliferation of GFAP-positive astrocytes encirling infiltrating lymphocytes around vessels. In the central nervous system, astrocytes and lympoid cells play an important role in the demarcation of cysts and local immunity, respectively. In conclusion, host tissue reaction in porcine cysticercosis seemed to vary significantly according to the affected organs of pigs. It is assumed that capsules containing worms seemed to be formed at early stage of cysticercosis.

• Applied Microscopy
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• v.44 no.1
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• pp.21-29
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• 2014

Retinal glial responses to hypertensive glaucomatous injury were spatiotemporally surveyed. Retinas as a whole or vertical sections were processed for anti-glial fibrillary acidic protein (GFAP), anti-Iba1, anti-nerve growth factor (NGF), and anti-tumor necrosis factor (TNF)-${\alpha}$ immunohistochemistry for confocal microscopic analyses. The optic nerve head of paired controls was processed for electron microscopy. GFAP positive astrocytes appeared in the nerve fiber layer in the glaucomatous and control retinas, changing from fine protoplasmic to stout fibrous parallel to glaucomatous duration. Iba1 positive microglia appeared in both retinas, and enormous reaction appeared at the latest glaucomatous. M$\ddot{u}$ller reaction detected by GFAP reactivity expanded from the end feet to whole profile following to duration in the glaucomatous. NGF reactivity expended from the end feet to the proximal radial processes of the M$\ddot{u}$ller cells in both retinas according to glaucomatous duration. TNF-${\alpha}$ immunoreactivity in the nerve fiber layer was stronger in both the glaucomatous and controls than in the normal, and exceptionally at the latest glaucomatous was even lower than the normal. The astrocytes in the optic nerve head are interconnected with each other via gap junction. These results demonstrate that astrocyte reaction propagates to the contralateral via physical links, and TNF-${\alpha}$ is correlated with NGF production for neuroprotection in response to hypertensive glaucomatous injury.

• Molecules and Cells
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• v.25 no.3
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• pp.376-384
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• 2008

The glial fibrillary acidic protein (GFAP) is traditionally used as a marker for astrocytes of the brain, and more recently for the hepatic stellate cells (HSCs) of the liver. Several GFAP splice variants have been previously reported in the astrocytes of the CNS and in the non-myelinating Schwann cells of the PNS. In this study, we investigate whether GFAP splice variants are present in the HSCs and their expression as a function of HSCs activation. Furthermore, the regulation of these transcripts upon treatment with interferon gamma ($IFN-{\gamma}$) will be explored. Using semi-quan-titative RT-PCR and real-time PCR, we examine the expression and regulation of GFAP splice variants in HSCs as well as their respective half-life. We discover that most of the GFAP splice variants ($GFAP{\alpha}$, ${\beta}$, ${\delta}$, ${\varepsilon}$ and $\kappa$) found in the neural system are also expressed in quiescent and culture-activated primary HSCs. Interestingly, $GFAP{\alpha}$ is the predominant form in quiescent and culture-activated primary HSCs, while $GFAP{\beta}$, predominates in the SV40-immortalized activated HSC-T6. $GFAP{\delta}$, ${\varepsilon}$ and ${\kappa}$ have similar half-lives of 10 hours, while $GFAP{\beta}$ has a half-life of 17 hours. Treatment of HSC-T6 with $IFN-{\gamma}$ results in a significant 1.29-fold up-regulation of $GFAP{\alpha}$ whereas the level of the other transcripts remains unchanged. In summary, $GFAP{\alpha}$, ${\beta}$, ${\delta}$, ${\varepsilon}$ and $\kappa$ are present in HSCs. They are differentially regulated on the transcription level, implying a role of the 5' and 3' untranslated regions.