• Korean Journal of Biological Psychiatry
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• v.24 no.1
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• pp.1-9
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• 2017

The proton magnetic resonance spectroscopy ($^1H-MRS$) is a tool used to detect concentrations of brain metabolites such as N-acetyl aspartate, choline, creatine, glutamate, and gamma-amino butyric acid (GABA). It has been widely used because it does not require additional devices other than the conventional magnetic resonance scanner and coils. Demyelination, or the neuronal damage due to loss of myelin sheath, is one of the common pathologic processes in many diseases including multiple sclerosis, leukodystrophy, encephalomyelitis, and other forms of autoimmune diseases. Rodent models mimicking human demyelinating diseases have been induced by using virus (e.g., Theiler's murine encephalomyelitis virus) or toxins (e.g., cuprizon or lysophosphatidyl choline). This review is an overview of the MRS findings on brain metabolites in demyelination with a specific focus on rodent models.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.345-351
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• 2002

The purpose of this study was to assess clinical proton MR spectroscopy (MRS) as a noninvasive method for evaluating brain tumor malignancy at 3T high field system. Using 3T MRI/MRS system, localized water-suppressed single-voxe1 technique in patients with brain tumors was employed to evaluate spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas were quantificated as a relative ratio. The variation of metabolites measurements of the designated region in 10 normal volunteers was less than 10%. Normal ranges of NAA/Cr and Cho/Cr ratios were 1.67${\pm}$018 and 1.16${\pm}$0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (p=0.005), but Cho/Cr ratio of all tumor tissue was significantly higher (p=0.001). Cho/Cr ratio of high-grade gliomas was significantly higher than that of low-grade gliomas (P=0.001). Except 4 menigiomas, lactate signal was observed in all tumor cases. The present study demonstrated that the neuronal degradation or loss was observed in all tumor tissues. Higher grade of brain tumors was correlated with higher Cho/Cr ratio, indicating a significant dependence of Cho levels on malignancy of gliomas. Our results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy.

• Biomedical Science Letters
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• v.21 no.1
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• pp.1-8
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• 2015

Alzheimer's disease is a common form of dementia occurring among the elderly population and can be identified by symptoms such as cognition impairments, memory loss and neuronal dysfunction. Alzheimer's disease was found to be caused by the deposition of $\beta$-amyloid plaques and neurofibrillary tangles. In addition, mutation in the APP (Amyloid precursor protein), Presenilin 1 (PSEN1) and Presenilin 2 (PSEN2) genes were also found to contribute to Alzheimer's disease. Since the potential conformational diagnosis of Alzheimer's disease requires histopathological tests on brain through autopsy, potential early diagnosis still remains challenging. In recent years, several researches have proposed the use of biomarkers for early diagnosis. In cerebrospinal fluid (CSF), $\beta$-amyloid(1-42), phosphorylated-tau and total tau were suggested to be effective biomarkers for Alzheimer's disease diagnosis. However, a single biomarker might not be sufficient for potential diagnosis of Alzheimer's disease. Thus, the use of RNA interference (RNAi) through microRNAs (miRNAs) has been proposed by several researchers for simultaneous analysis of several biomarkers using microarray technology. These miRNA based biomarkers can be analysed from both blood and CSF, but miRNAs from blood are advantageous over CSF as they are non-invasive and simple for collection. Moreover, the RNAi based therapeutics by siRNA (short interference RNA) or shRNA (short hairpin RNA) have also been proposed to be effective in the treatment of Alzheimer's disease. This review describes the promising application of RNAi technology in therapeutics and as a biomarker for both Alzheimer's disease diagnosis and treatment.

• Journal of Korean Neurosurgical Society
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• v.37 no.2
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• pp.124-128
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• 2005

Objective: Congenital bilateral perisylvian syndrome(CBPS) has been defined as a characteristic malformative perisylvian polymicrogyria(PMG) in patients with clinical symptoms of pseudobulbar palsy and epileptic seizures. For the present study, we investigate clinicopathologic features of CBPS associated with timing of lesion formation. Methods: Clinicopathologic features of CBPS from 6 patients with surgical resection of the cerebral lesions due to medically intractable seizures were studied. Results: Seizure onset ranged from 1 to 10years (average 6.7years) of age, and average duration of seizure was 23years. All had complex partial seizures, and two patients had additional tonic clonic seizures. Magnetic resonance (MR) images showed polymicrogyria, atropic gyri with gliosis. In the histopathologic examination, the cortical lesions revealed features of ulegyria; atrophic and sclerotic gyri, laminar loss of neurons, extensive lobular gliosis throughout the gray and white matter, neuronoglial nodule formation, and many amyloid bodies. Unlayered or four-layered PMG was not identified. Conclusion: Above data suggest that CBPS might be caused by ulegyria resulting from developmental cortical defect during early fetal stage or acquired hypoxic/ischemic injury in prenatal or postnatal life.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.51-58
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• 2006

The promoting effect of hydrogen peroxide ($H_2O_2$) against the cytotoxicity of 1-methyl-4-phenylpyridinium ($MPP^+$) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with $MPP^+$ resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. Addition of $H_2O_2$ enhanced the $MPP^+-induced$ nuclear damage and cell death. Catalase, Carboxy-PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the cytotoxic effect of $MPP^+$ in the presence of $H_2O_2$. Addition of $H_2O_2$ promoted the change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to $MPP^+$ in PC12 cells. The results show that the $H_2O_2$ treatment promotes the cytotoxicity of $MPP^+$ against PC12 cells. $H_2O_2$ may enhance the $MPP^+$-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of ROS and depletion of GSH. The findings suggest that $H_2O_2$ as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by neurotoxins.

• YAKHAK HOEJI
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• v.60 no.2
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• pp.92-99
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• 2016

Parkinson's disease (PD) is one of the representative neurodegenerative movement disorders with the selective loss of dopaminergic neurons in the substantia nigra. 6-Hydroxydopamine (6-OHDA) is widely used as an experimental model system to mimic PD and has been reported to cause neuronal cell death via oxidative and/or nitrosative stress. Therefore, daily intake of dietary or medicinal plants which fortifies cellular antioxidant capacity can exert neuroprotective effects in PD. In the present study, we have investigated the protective effect of Korean red ginseng (KRG) against 6-OHDA-induced nitrosative death in C6 glioma cells. Treatment of C6 cells with 6-OHDA decreased cell viability and increased expression of inducible nitric oxide synthase, production of nitric oxide as well as peroxynitrite, and formation of nitrotyrosine. 6-OHDA led to apoptotic cell death as determined by decreased Bcl-2/Bax, phosphorylation of JNK, activation of caspase-3, and cleavage of PARP. Conversely, pretreatment of C6 cells with KRG attenuated 6-ODHA-induced cytotoxicity, apoptosis, and nitrosative damages. To further elucidate the molecular mechanism of KRG protection against 6-OHDA-induced nitrosative cell death, we have focused on the cellular self-defense molecules against exogenous noxious stimuli. KRG treatment up-regulated heme oxygenase-1 (HO-1), a key antioxidant enzyme essential for cellular defense against oxidative and/or nitrosative stress via activation of Nrf2. Taken together, these findings suggest KRG may have preventive and/or therapeutic potentials for the management of PD.

• Korean Journal of Acupuncture
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• v.24 no.1
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• pp.131-144
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• 2007

Objectives : Although the cause of neuronal death of Parkinson's disease remains unclear, increasing evidence points to the role of inflammatory processes. And the hallmark of brain inflammation is the activation of microglia. This study was performed to prove the effect of acupuncture on inhibiting microglial activation. Methods : The rat models which were injected with 6-hydroxydopamine were treated with acupuncture once a day on LR3 (太衝) and GB34 (陽陵泉). To prove the effect of inhibiting microglial activation, we examined the tyrosine hydroxylase (TH) immunopositive neurons and CD11b immunohistochemistry in the substantia nigra. Results : There were 18% (third day), 32% (seventh day) loss of TH-positive cell bodies in the control group and 23% (third day), 26% (seventh day) in the acupuncture group, whereas 3% (third day), 10% (seventh day) in vehicle group. The difference of optical density in substantia nigra was evaluated by subtracting log inverse gray value of contralateral side from that of ipsilateral side. With regards to the result of CD11b immunohistochemistry, acupuncture group showed significantly inhibited microglial activation compared with control group (p<0.01) on the seventh day. Conclusions : Acupuncture showed the effect of inhibition of microglial activation in seventh day. However, the effect of protection of TH positive cell bodies was not shown. So we need longer investigation of the effect of acupuncture on Parkinson's disease.

• Journal of the Optical Society of Korea
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• v.18 no.1
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• pp.55-59
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• 2014

Sarcopenia, or reduced muscle mass and volume, is due to various factors such as senile change, neuronal degeneration, drug, malignancy, and sepsis. Sarcopenia with the aging process has been evidenced by the decline in muscle mass by 0.5 to 1% per year with 3-5% reduction in muscle strength for 10 years between the ages of 40 and 50, and a 1-2% of decline of mass every year in people aged 60-70. Therefore, early diagnosis and understanding the mechanism of sarcopenia are crucial in the prevention of muscle loss. However, it is still difficult to image changes of muscle microstructure due to a lack of techniques. In this study, we developed an animal model using denervated rats to induce a rapid atrophy in the tibialis anterior (TA) and imaged its structural changes using optical coherence tomography (OCT) along with histologic and ultrasound analyses. Ultrasound showed changes of overall muscle size. Histology revealed that the atrophic TA muscle displayed an increased size variability of muscle fiber and inflammatory changes. Three dimensional OCT imaged the changes of perimysial grid and muscle fiber structure in real time without sacrifice. These observed advantages of multimodal imaging using OCT and ultrasound would provide clinical benefits in the diagnosis of sarcopenia.

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.41-46
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• 2005

Objective : A study of the histopathologic and neurobehavioral correlates of cortical impact injury produced by increasing impact velocity using the controlled cortical impact[CCI] injury model is studied. Methods : Twenty-four Sprague-Dawley rats [$200{\sim}250g$] were given CCI injury using a pneumatically driven piston. Effect of impact velocity on a 3mm deformation was assessed at 2.5m/sec [n=6], 3.0m/sec [n=6], 3.5m/sec [n=6], and no injury [n=6]. After postoperative 24hours the rats were evaluated using several neurobehavioral tests including the rotarod test, beam-balance performance, and postural reflex test. Contusion volume and histopathologic findings were evaluated for each of the impact velocities. Results : On the rota rod test, all the injured rats exhibited a significant difference compared to the sham-operated rats and increased velocity correlated with increased deficit [p<0.001]. Contusion volume increased with increasing impact velocity. For the 2.5, 3.0, and 3.5m/sec groups, injured volumes were $18.8{\pm}2.3mm^3$, $26.8{\pm}3.1mm^3$, and $32.5{\pm}3.5mm^3$, respectively. In addition, neuronal loss in the hippocampal sub-region increased with increasing impact velocity. In the TUNEL staining, all the injured groups exhibited definitely positive cells at pericontusional area. However, there were no significant differences in the number of positive cells among the injured groups. Conclusion : Cortical impact velocity is a critical parameter in producing cortical contusion. Severity of cortical injury is proportional to increasing impact velocity of cortical injury.

• The Korean Journal of Pain
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• v.32 no.4
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• pp.271-279
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• 2019

Background: We utilized diffusion tensor imaging (DTI) to evaluate the cerebral white matter changes that are associated with phantom limb pain in patients with unilateral arm amputation. It was anticipated that this would complement previous research in which we had shown that changes in cerebral blood volume were associated with the cerebral pain network. Methods: Ten patients with phantom limb pain due to unilateral arm amputation and sixteen healthy age-matched controls were enrolled. The intensity of phantom limb pain was measured by the visual analogue scale (VAS) and depressive mood was assessed by the Hamilton depression rating scale. Diffusion tensor-derived parameters, including fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD), were computed from the DTI. Results: Compared with controls, the cases had alterations in the cerebral white matter as a consequence of phantom limb pain, manifesting a higher AD of white matter in both hemispheres symmetrically after adjusting for individual depressive moods. In addition, there were associations between the RD of white matter and VAS scores primarily in the hemispheres related to the missing hand and in the corpus callosum. Conclusions: The phantom limb pain after unilateral arm amputation induced plasticity in the white matter. We conclude that loss of white matter integrity, particularly in the hemisphere connected with the missing hand, is significantly correlated with phantom limb pain.