• The Korea Journal of Herbology
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• v.20 no.4
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• pp.121-132
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• 2005

Objectives : Siegesbeckiae Herba's effect on the protection of nerve cells was tested, and the effects were compared between Siegesbeckia glabrescens Makino, the state of which is spica imported from China, and original Korean leaves of it. Methods : After damaging nerve cells by exposing them on NMDA (N-methyl-D-aspartic acid) and KA(kainic acid), Siegesbeckiae Herba's effect on cell death, inhibition rate, glutamate separation, and ROS(reactive oxygen species) production were examined. Results : 1. Siegesbeckiae Herba inhibited the cell death exposed to NMDA. 2. Siegesbeckiae Herba inhibited the amount of glutamate separated from nerve cells exposed to NMDA. 3. Siegesbeckiae Herba inhibited the production of ROS induced by NMDA. 4. Siegesbeckiae Herba did not inhibit the cell death exposed to KA. 5. Chinese Siegesbeckiae Spica had no inhibition effect on cell death. Conclusions : Siegesbeckiae Herba was effective in inhibiting the death of nerve cells exposed to NMDA, and in protecting nerve cells from various damages in nerve cell diseases. Because Chinese Siegesbeckiae Spica did not show such effects, it is necessary to closely examine those effects according to the used parts.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.95-95
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• 1995

뇌신경 변성 / 퇴행과 관련된 중요한 병인론 중의 하나는 변성 과정에서 형성된 유리기(free radical)로 인한 항산화계의 평형 소실로 알려져 있다. Aspalatone (APT)의 예상되는 항산화 효능을 검정하기 위하여 본 실험에서는 Kainic acid (KA) 유발 뇌변성 모델을 적용하였다. KA 모델은 변연계의 간질성 경련과 신경세포 변성에 대하여 재현성 있는 병변 모델을 제공해 주며, 이와 같은 신경세포의 병독 기전에 산소 유리기가 관여함이 강력히 시사되고 있기 때문이다. KA 투여로 인하여 지속적이고도 전형적인 간질성 경련이 관찰되고 1일 이내에 높은 치사율을 보였으나 APT으로 인하여 그 간질성 경련 행위와 비율이 억제되고 KA 유발 치사율도 억제되었다. 최종 KA 투여 3일 후에 얻어진 흰쥐 해마 및 대뇌 피질에서 항산화 효소인 Superoxide dismutase (SOD), Catalase (Cat.), Glutathione peroxidase (GSH-PX) 및 과산화지질의 지표인 Malondialdehyde (MDA)를 검정하였다. 대조군에 비하여 KA는 뇌조직의 SOD-1을 유도하였으나, Cat.와 GSH-PX의 활성은 현저히 유도되지 않았고, 반면에 MDA 치는 현저히 증가하였다. 즉, Cat., GSH-PX와 같은 $H_2O$$_2$중화제가 동반 유도하지 않는 SOD의 유도는 세포내 축적되는 $H_2O$$_2$로 인하여 Fenton/Haber-Weiss 반응을 가속화하여 과산화지질화를 촉진함을 시사한다. APT 병용 투여로 SOD는 현저히 유도되지 않았으나 특히 Cat.가 현저히 유도되어지고 MDA는 억제되었다. 이와 같은 생화학적인 결과는 다음의 형태학적인 소견과 일치한다. Fos 관련 항원 (FRA)와 SOD-1을 면역세포화학 (Immunocytochemistry)적 방법으로 이중 표식 (double-labelling) 하였다. FRA는 KA로 인한 신경세포의 자극에 대한 지표로 응용하였고, SOD-1은 퇴행성 뇌질환에서 산화적 손상의 지표로 사용하였다. KA 투여로 해마의 dentate gyrus (DG) 내에 강한 면역환성 (immunoreactivity)이 나타났고 pyramidal cell layer (PCL)와 glia에 SOD-1이 강하게 염색되었다. APT 병용 투여로 상당수의 경련이 일어나지 않은 흰쥐는 해마의 DG에 FRA가 경미하게 염색되었고, PCL에 SOD-1도 경미하게 나타났으나, 경련이 나타난 쥐에서는 KA만을 투여한 흰쥐와 구별되지 않았다. 이상의 APT의 항산화 효과는 KA로 인한 뇌세포 변성 개선에 중요한 인자로 작용할 것으로 사료되나, 보다 명확한 APT의 기전을 검색하고 직접 임상에 응응하기 위하여는 보다 다양한 실험 조건이 보완되어야 찰 것으로 생각된다.

• Molecules and Cells
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• v.37 no.4
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• pp.345-355
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• 2014

Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing ($GFAP^+$) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, $GFAP^+$ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including $S100{\beta}$, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.

• Korean Journal of Acupuncture
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• v.29 no.3
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• pp.396-405
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• 2012

Objectives : To confirm whether acupuncture can suppress the degree of seizure and the activation of astrocytes in hippocampi using kainic acid(KA)-induced epilepsy mouse model. Methods : 8 weeks C57BL/6 mice(20~25 g) were given acupuncture once a day at acupoint HT8(Shaofu) bilaterally during 2 days before KA injection. After an intraperitoneal injection of 30 mg/kg KA, acupuncture treatment was subsequently administered once more(total 3 times), and the degree of seizure was observed for 120 min. The neuronal cell death, pERK expression, and astrocyte activation confirmed 1 hour and 24 hours after KA injection. Results : Acupuncture treatment at HT8 suppressed KA-induced epileptic seizure. One hour after KA injection, the pERK expression was increased, which was reduced by the acupuncture treatment. Twenty four hours after injection, the treatment decreased the KA-induced neuronal cell death, the interleukin-$1{\beta}$ expression and the astrocyte activation in the CA3 region of the mouse hippocampus. Conclusions : Acupuncture treatment at HT8 decreases the KA-induced epileptic seizure, the neural cell inflammation and death.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.1
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• pp.37-43
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• 2010

The serine/threonine kinase Akt has been shown to play a role of multiple cellular signaling pathways and act as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI3K). It has been reported that phosphorylated Akt activates eNDS resulting in the production of NO and that NO stimulates soluble guanylate cyclase (sGC), which results in accumulation of cGMP and subsequent activation of the protein kinase G (PKG). It has been also reported that PKG activates PI3K/Akt signaling. Therefore, it is possible that PI3K, Akt, eNOS, sGC, and PKG form a loop to exert enhanced and sustained activation of Akt. However, the existence of this loop in eNOS-expressing cells, such as endothelial cells or astrocytes, has not been reported. Thus, we examined a possibility that Akt phosphorylation might be enhanced via eNOS/sGC/PKG/PI3K pathway in astrocytes in vivo and in vitro. Phosphorylation of Akt was detected in astrocytes after KA treatment and was maintained up to 72 h in mouse hippocampus. 2 weeks after KA treatment, astrocytic Akt phosphorylation was normalized to control. The inhibition of eNOS, sGC, and PKG significantly decreased Akt and eNDS phosphorylation induced by KA in astrocytes. In contrast, the decreased phosphorylation of Akt and eNDS by eNDS inhibition was significantly reversed with PKG activation. The above findings in mouse hippocampus were also observed in primary astrocytes. These data suggest that Akt/eNOS/sGC/PKG/PI3K pathway may constitute a loop, resulting in enhanced and sustained Akt activation in astrocytes.

• Proceedings of the PSK Conference
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• 2005.04a
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• pp.99-101
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• 2005

• Journal of Microbiology
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• v.43 no.2
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• pp.213-218
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• 2005

Epilepsy constitutes a significant public health problem, and even the newest drugs and neurosurgical techniques have proven unable to cure the disease. In order to select a group of isolates which could generate an active compound with neuroprotective or antiepileptic properties, we isolated 517 actinomycete strains from soil samples taken from Jeju Island, in South Korea. We then screened these strains for possible anti-apoptotic effects against serum deprivation-induced hippocampal cell death, using the 3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay as an in vitro test. The excitotoxic glutamate analog, kainic acid (KA), was used to induce seizures in experimental mice in our in vivo tests. As a result of this testing, we located one strain which exhibited profound neuroprotective activity. This strain was identified as a Streptomyces species, and exhibited the rifampinresistant genotype, Asn$(AAC)^$442, according to the results of 16S rRNA and rpoB gene analyses