• The Korean Journal of Physiology and Pharmacology
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• 제8권5호
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• pp.245-251
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• 2004

The effects of fetal mesencephalic cell grafts on the restoration of nigrostriatal dopaminergic function were studied in the intrastriatal 6-hydroxydopamine-lesioned rats. Four weeks after lesioning, transplantation of ventral mesencephalic cells from embryonic day 14 fetuses showed the number of tyrosine hydroxylase (TH) positive cells and fiber outgrowth in the grafted striatum, and significantly ameliorated symptomatic motor behavior of the animals, as determined by apomorphine-induced rotation. Furthermore, in substantia nigra pars compacta (SNc), the numbers of TH + cells and fibers were markedly restored. Dopamine content of ipsilateral SNc was close to that of contralateral SNc $(91.9{\pm}9.8%)$ in the transplanted animals, while the ratio was approximately 32% in sham-grafted animals. These results indicate that grafted cells restored the activity for the dopaminergic neurons located in SNc, although they were transplanted into striatum. In addition, we showed that the implanted fetal cells expressed high level of glial cell line-derived neurotrophic factor (GDNF), suggesting that the transplanted fetal cells might serve as a dopamine producer and a reservoir of neurotrophic factors. These results may be helpful in consideration of the therapeutic transplantation at early stage of PD.

• Journal of Acupuncture Research
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• 제26권1호
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• pp.173-185
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• 2009

Objectives : Amyotrophic Lateral Sclerosis(ALS) is a progressive disease that causes degeneration of the motor neurons of the brain and spinal cord. The purpose of this case study is to improvement of oriental mediacl treatment on ALS. Methods : The patients were treated by acupuncture, moxibustion, cupping therapy, herbal medication, physical treatment. To determine the effects of Oriental medical treatment, we evaluated weekly used by Korean version of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(K-ALSFRS-R), Amyotrophic Lateral Sclerosis Severity Scale(ALSSS). Results : Symptoms such as cervical and shoulder pain, knee pain, cold sweating, insomnia etc were improved after above treatment. But K-ALSFRS-R and ALSSS were no improvement after above treatment. Conclusions : The Oriental medical treatment is effective on local symptoms of ALS, but there were no functional improvement of ALS in this case study. It is necessary to have more examination about ALS.

• The Korean Journal of Pain
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• 제29권1호
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• pp.3-11
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• 2016

A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration.

• 구강회복응용과학지
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• 제33권1호
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• pp.1-6
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• 2017

보툴리눔 독소 주사는 이마, 눈가 주름치료 등 미용성형분야 뿐만 아니라 만성 편두통(chronic migraine), 근육긴장이상(dystonia), 경직(spasticity), 측두하악장애의 치료 등에 사용되어 왔다. 특히 보툴리눔 독소 주사는 만성편두통환자의 예방적 치료요법으로 현재까지 유일하게 승인된 요법이다. 기존에 잘 알려진 운동신경에서의 마비효과와는 달리, 편두통에 대한 작용기전은 감각신경에서 말초감작과 신경원성염증과 관련되는 substance P, CGRP, glutamate 등 비콜린성 신경전달물질의 유리를 차단하여 통증신호를 차단하는 역할을 한다는 가설이 제기되고 있다. 본 논문에서는 보툴리눔독소가 갖는 진통효과에 대한 고찰과 함께 이를 통하여 추후 만성편두통환자에 대한 주사법 개발에 대한 방향성을 제시하고자 한다.

• BMB Reports
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• 제43권11호
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• pp.756-760
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• 2010

Recent studies have reported that delayed-rectifier Kv channels regulate apoptosis in the nervous system. Herein, we investigated changes in the expression of the delayed-rectifier Kv channels Kv1.2, Kv2.1, and Kv3.1 after acute spinal cord injury (SCI) in rats. We performed RT-PCR analysis and found an increase in the level of Kv2.1 mRNA after SCI but no significant changes in the levels of Kv1.2 and Kv3.1 mRNA. Western blot analysis revealed that Kv2.1 protein levels rapidly decreased and then dramatically increased from 1 day, whereas Kv3.1b protein levels gradually and sharply decreased at 5 days. Kv1.2 protein levels did not change significantly. In addition, Kv2.1 clusters were disrupted in the plasma membranes of motor neurons after SCI. Interestingly, the expressional changes and translocation of Kv2.1 were consistent with the apoptotic changes on day 1. Therefore, these results suggest that Kv2.1 channels probably contribute to neuronal cell responses to SCI.

• 동의생리병리학회지
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• 제19권6호
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• pp.1666-1672
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• 2005

Oriental medicinal drugs have a broad spectrum of clinical use for the cure of nervous system diseases including brain ischemic damages or neuropathies. Yet, specific drugs or drug components used in the oriental medicine in relation to none fiber regeneration are not known. In the present study, possible growth promoting effects of oriental medicinal drugs were investigated in the injured sciatic nerve system in the rat. By immunofluorescence staining, we found that Jahageo (JHG, Hominis placenta) increased Induction levels of axonal growth associated protein GAP-43 in the rat sciatic none. Small growth promoting activity was found in Golsebo (GSB, Drynariae rhizoma) and Baikhasuo (BHSO, Polygoni multiflori radix) drugs. JHG also increased cell cycle protein Cdc2 levels in the injured area of the sciatic nerves. Immunofluorescence staining indicated that induced Cdc2 protein was mostly localized in the Schwann cells in the injury area, implying that JHG activity might be related to increased Schwann cell proliferation during axonal regeneration. Moreover, levels of phospho-extracellular signal-regulated (ERK) pathway in the injured neNes were elevated by JHG treatment while levels of total ERK were unaltered. In vivo measurement of axonal regeneration using retrograde tracer showed that JHG, GSB and BHSO significantly enhanced Dil-labeled regenerating motor neurons compared with saline control. The present data suggest that oriental medicinal drugs such as JHG, GSB, and BHSO may be a useful target for developing specific drugs of axonal regeneration.

• Molecules and Cells
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• 제22권1호
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• pp.51-57
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• 2006

Haloperidol is a classical neuroleptic drug that is still in clinical use and can lead to abnormal motor activity following repeated administration. However, there is little knowledge of how it triggers neuronal impairment. In this study, we report that it induced calcium ion influx via L-type calcium channels and that the elevation of calcium ions induced by haloperidol appeared to render hippocampal cells more susceptible to oxidative stress. Indeed, the level of cytotoxic reactive oxygen species (ROS) and the expression of pro-apoptotic Bax increased in response to oxidative stress in haloperidol-treated cells, and these effects were inhibited by verapamil, a specific L-type calcium channel blocker, but not by the T-type calcium channel blocker, mibefradil. These findings indicate that haloperidol induces calcium ion influx via L-type calcium channels and that this calcium influx influences neuronal fate.

• Journal of Ginseng Research
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• 제39권2호
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• pp.148-154
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• 2015

Background: Ginseng is known to have antiapoptotic, anti-inflammatory, and antioxidant effects. The present study investigated a possible role of Korean Red Ginseng (KRG) in suppressing dopaminergic neuronal cell death and the cleavage of p35 to p25 in the substantia nigra (SN) and striatum (ST) using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Methods: Ten-week-old male C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 d, and then administered KRG (1 mg/kg, 10 mg/kg, or 100 mg/kg) once a day for 12 consecutive days from the first injection. Pole tests were performed to assess the motor function of the mice, dopaminergic neuronal survival in the SN and ST was evaluated using tyrosine hydroxylase-immunohistochemistry, and the expressions of cyclin-dependent kinase 5 (Cdk5), p35, and p25 in the SN and ST were measured using Western blotting. Results: MPTP administration caused behavioral impairment, dopaminergic neuronal death, increased Cdk5 and p25 expression, and decreased p35 expression in the nigrostriatal system of mice, whereas KRG dose-dependently alleviated these MPTP-induced changes. Conclusion: These results indicate that KRG can inhibit MPTP-induced dopaminergic neuronal death and suppress the cleavage of p35 to p25 in the SN and the ST, suggesting a possible role for KRG in the treatment of Parkinson's disease.

• Journal of Ginseng Research
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• 제42권4호
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• pp.429-435
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• 2018

Background: Recent studies have shown that Korean Red Ginseng (KRG) successfully protects against dopaminergic neuronal death in the nigrostriatal pathway of a Parkinson's disease (PD) mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration; however, the mechanism has yet to be identified. Therefore, in this study we used two-dimensional electrophoresis to investigate the effects of KRG on the changes in protein expression in the substantia nigra (SN) of MPTP-treated mice. Methods: Male C57BL/6 mice (9 wk old) were intraperitoneally administered MPTP (20 mg/kg) four times at 2-h intervals, after which KRG (100 mg/kg) was orally administered once a day for 5 d. Two hours after the fifth KRG administration, a pole test was conducted to evaluate motor function, after which the brains were immediately collected. Survival of dopaminergic neurons was measured by immunohistochemistry, and protein expression was measured by two-dimensional electrophoresis and Western blotting. Results: KRG alleviated MPTP-induced behavioral dysfunction and neuronal toxicity in the SN. Additionally, the expression of eight proteins related to neuronal formation and energy metabolism for survival were shown to have changed significantly in response to MPTP treatment or KRG administration. KRG alleviated the downregulated protein expression following MPTP administration, indicating that it may enhance neuronal development and survival in the SN of MPTP-treated mice. Conclusion: These findings indicate that KRG may have therapeutic potential for the treatment of patients with PD.

• Journal of Ginseng Research
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• 제42권3호
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• pp.379-388
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• 2018

Background: Ginsenosides are the main ingredients of Korean Red Ginseng. They have extensively been studied for their beneficial value in neurodegenerative diseases such as Parkinson's disease (PD). However, the multitarget effects of Korean Red Ginseng extract (KRGE) with various components are unclear. Methods: We investigated the multitarget activities of KRGE on neurological dysfunction and neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. KRGE (37.5 mg/ kg/day, 75 mg/kg/day, or 150 mg/kg/day, per os (p.o.)) was given daily before or after MPTP intoxication. Results: Pretreatment with 150 mg/kg/day KRGE produced the greatest positive effect on motor dysfunction as assessed using rotarod, pole, and nesting tests, and on the survival rate. KRGE displayed a wide therapeutic time window. These effects were related to reductions in the loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons, apoptosis, microglial activation, and activation of inflammatory factors in the substantia nigra pars compacta and/or striatum after MPTP intoxication. In addition, pretreatment with KRGE activated the nuclear factor erythroid 2-related factor 2 pathways and inhibited phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways, as well as blocked the alteration of blood-brain barrier integrity. Conclusion: These results suggest that KRGE may effectively reduce MPTP-induced neurotoxicity with a wide therapeutic time window through multitarget effects including antiapoptosis, antiinflammation, antioxidant, and maintenance of blood-brain barrier integrity. KRGE has potential as a multitarget drug or functional food for safe preventive and therapeutic strategies for PD.