• BMB Reports
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• 제49권2호
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• pp.71-72
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• 2016

Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients.

• The Journal of Korean Physical Therapy
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• 제24권4호
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• pp.262-267
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• 2012

Purpose: This study was designed to analyze the differences in cerebral cortex activity of the elderly after extracting the movement related cortical potentials (MRCPs) from electroencephalogram (EEG) during a concentric and eccentric contraction of the elbow joint flexors, and entering them into the brain-mapping program to make the images. Methods: Right-dominant normal elderly people were divided into an eccentric contraction group and a concentric contraction group. Then, their MRCPs were measured using EEG and sEMG, during an eccentric and concentric contraction. Then, they were converted into images using the brain-mapping program. Results: Eccentric contraction group's $C_3$ and Cz showed statistically higher mean values of MRCP positive potential than the concentric contraction group. Conclusion: Researching a cerebral cortex activity, using MRCP, would provide basic data for clinical neuro-physiological researches on aging or neural plasticity of patients with a central nervous system injury.

• 약학회지
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• 제43권4호
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• pp.535-540
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• 1999

Glutamate (Glu) receptor-mediated excitoxicity has been implicated in many acute and chronic types of neurological disorders. Exposure of mature rat cortical neurons (15-18 days in culture) to the various concentrations of Glu resulted in a marked neuronal death, whereas immature rat cortical neurons (4∼5 days in culture) were resistant to the Glu-induced toxicity. Glu receptor subtype-specific agonists showed differential extent of toxicity in the immature neurons. The neurons treated with NMDA or kainate (KA) did not exhibit damage. However, quisqualate (QA) treatment induced a considerable cell death (36.1%) in immature enurons. The non-NMDA antagonist DNQX did not reduce this response. Interestingly, the QA-induced toxicity was potentiated by spermine in a concentration-dependent manner. Again, the spermine-enhanced damage was not altered by the polyamine antagonist ifenprodil. Taken together, unlike NMDA or KA, QA can induce neurotoxicity in immature rat cortical neurons and the QA-induced toxicity was potentiated by spermine. The lack of antagonizing effects of DNQX and ifenprodil on QA-induced toxicity and the potentiated toxicity by spermine, respectively, implies that both QA receptor and the polyamine site of NMDA receptor may not mediate the neurotoxicity observed in this study, and that a distinct mechanism(s) may be involved in excitotoxicity in immature neurons.

• 대한약리학회지
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• 제32권2호
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• pp.169-175
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• 1996

The reactivity of the sulfhydryl (thiol) group of homocysteine has been associated with an Increased risk of atherosclerosis, thrombosis and stroke. Thiols also react with nitric oxide (NO, an endothelium-derived relaxing factor (EDRF) ), forming S-nitrosothiols that have been reported to have potent vasodilatory and antiplatelet effects and been expected to decrease adverse vascular effects of homocysteine. The present study was aimed to Investigate whether the S-nitrosation of homocysteine modulates the neurotoxic effects of homocysteine. An 18 hour-exposure of cultured rat cortical neurons to homocysteine ( >1 mM) resulted in a significant neuronal cell death. At comparable concentrations ( <10 mM), however, S-nitrosohomocysteine did not induce neuronal cell death. Furthermore, S-nitrosohomocysteirle partially blocked NMDA-mediated neurotoxicity. S-nitrosohomocysteine also decreased NMDA-mediated increases in intracellular calcium concentration. The present data indicate that in brain nitric oxide produced from neuronal and nonneuronal cells can modulate the potential, adverse properties of homocysteine.

• 대한한의학회지
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• 제24권3호
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• pp.72-83
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• 2003

Objective : The goal of the present study was to investigate the protective effect of Gamiheechum-tang (Jiaweixiqian-tang; GHCT) on brain tissue damage from chemical or ischemic insults. Methods : Levels of cultured cortical neuron death caused by toxic chemicals were measured by LDH release assay. Neuroprotective effects of GHCT on brain tissues were examined in vivo by ischemic model of middle cerebral artery (MCA) occlusion. Results : Animal groups treated with GBCT showed significantly decreased hypertension, and reduced levels of aldosterone, dopamine, and epinephrine in the plasma. GHCT treatments ($l0-200\mu\textrm{g}/ml$) significantly decreased cultured cortical neuron death mediated by AMPA, kainate, BSO, or Fe2+ when measured by LDH release assay. Yet, cell death mediated by NMDA was effectively protected by GHCT at the highest concentration examined ($200\mu\textrm{g}/ml$). In the in vivo experiment examining brain damage by MCA occlusion, affected brain areas by ischemic damage and edema were significantly less in animal groups administered with GHCT compared to the non-treated control group. Neurological examinations of forelimbs and hindlimbs showed that GHCT treatment improved animals' recovery from ischemic injury. Moreover, the extent of injury in cortical and hippocampal pyramidal neurons in ischemic rats was much reduced by GHCT, whose morphological features were similarly observed in non-ischemic animals. Conclusion : The present data suggest that GBCT may play an important role in protecting brain tissues from chemical or ischemic injuries.

• 한국지능시스템학회논문지
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• 제23권6호
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• pp.565-570
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• 2013

영장류 대뇌 피질 영역 중 거울 뉴런들이 분포한 것으로 추정되는 몇몇 영역은 목적성 행위에 대한 시각 정보를 기반으로 모방학습을 수행함으로써 관측 행동의 의도 인식 기능을 담당한다고 알려졌다. 본 논문은 이러한 거울 뉴런 영역을 모델링 하여 인간-로봇 상호작용 시스템에 적용함으로써, 자동화 된 의도인식 시스템을 개발하고자 한다. 거울 뉴런 시스템 계산 모델은 동적 신경망을 기반으로 구축하였으며, 모델의 입력은 객체와 행위자 동작에 대한 연속된 특징 벡터 집합이고 모델의 모방학습 및 추론과정을 통해 관측자가 수행할 수 있는 움직임 정보를 출력한다. 이를 위해 제한된 실험 공간 내에서 특정 객체와 그에 대한 행위자의 목적성 행동, 즉 의도에 대한 시나리오를 전제로 키넥트 센서를 통해 모델 입력 데이터를 수집하고 가상 로봇 시뮬레이션 환경에서 대응하는 움직임 정보를 계산하여 동작을 수행하는 프레임워크를 개발하였다.

• PNF and Movement
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• 제1권1호
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• pp.19-25
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• 2003

Objectives: The purpose of this article is to summarize the effect of stretch stimulus on muscle contraction facilitation. Methods : Some studies of the stretch reflex. ${\gamma}-motor$ system, and the effect of stretch stimulus on muscle activation were reviewed. Results : To facilitate muscle contraction, before the movement is started, the prime mover is in stretched position. The patient must be instructed to occur voluntary muscle contraction after quick stretching. It elicits the functional stretch reflex to produce a more powerful and functional contraction. The intensity of muscle contraction depends on two ways. One is firing rate of ${\alpha}-motor$ neuron by sensory information from the periphery induced in stretched position and stretch reflex. The other is excitation level of the cortical motor area and the corresponding motor neurons. Conclusions: To activate central nervous system and to increase firing rate of ${\alpha}-motor$ neuron. the therapist should apply quick stretch for the patient with stretched position and the patient should make voluntary muscle contraction.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.39-47
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• 2010

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.

• 생명과학회지
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• 제18권3호
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• pp.311-317
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• 2008

Pathophysiological oxidative stress results in neuronal cell death mainly due to the generation reactive oxygen species (ROS). In low oxygen situation such as hypoxia and ischemia, excessive ROS is generated. Coptidis Rhizoma (CR) is a traditional medicine used for the incipient stroke. In this report we show that CR water extracts $(1\;{\mu}g/ml)$ exhibited protective effects of neuronal cell death in a hypoxic model (2% $O_2/5%\;CO_2,\;37^{\circ}C,$ 3 hr) of cultured rat cortical cells. We further show that CR water extracts significantly reduced the intensity of green fluorescence after staining with $H_2DCF-DA$ on one hour and three days after hypoxic shock and in normoxia as well. Our results indicate that CR water extracts prevent neuronal death by suppressing ROS generation.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.145-145
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• 2003