• 한국의학물리학회지:의학물리
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• 제33권4호
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• pp.88-100
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• 2022

Purpose: Cerebral microbleeds are more susceptible than surrounding tissues and have been associated with a variety of neurological and neurodegenerative disorders that are indicative of an underlying vascular pathology. We investigated relaxivity changes and microvascular indices in the presence of microbleeds in an imaging voxel by evaluating those before and after contrast agent injection. Methods: Monte Carlo simulations were run with a variety of conditions, including different magnetic field strengths (B₀), different echo times, and different contrast agents. ΔR2^* and ΔR2 and microvascular indices were calculated with varying microvascular vessel sizes and microbleed loads. Results: As B₀ and the concentration of microbleeds increased, 𝜟R2^* and 𝜟R2 increased. 𝜟R2^* increased, but 𝜟R2 decreased slightly as the vessel radius increased. When the vessel radius was increased, the vessel size index (VSI) and mean vessel diameter (mVD) increased, and all other microvascular indices except mean vessel density (Q) increased when the concentration of microbleeds was increased. Conclusions: Because patients with neurodegenerative diseases often have microbleeds in their brains and VSI and mVD increase with increasing microbleeds, microbleeds can be altered microvascular signals in a voxel in the brain of a neurodegenerative disease at 3T magnetic resonance imaging.

• IMMUNE NETWORK
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• 제4권1호
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• pp.60-64
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• 2004

Background: Microglial cells, major immune effector cells in the central nervous system, become activated in neurodegenerative disorders. Activated microglial cells produce proinflammatory mediators such as nitric oxide (NO), tumor necrosis factor-$\alpha$ and interleukin-$1{\beta}$(IL-$1{\beta}$). These proinflammatory mediators have been shown to be significantly increased in the neurodegenerative disorders such as Alzhimer's disease and Pakinson's disease. It was known that one of the neurodegeneration source is stress and it is important to elucidate mechanisms of the stress response for understanding the stress-related disorders and developing improved treatments. Because one of the neuropeptide which plays a main role in regulating the stress response is corticotropin-releasing hormone (CRH), we analyzed the regulation of NO release by CRH in BV2 murine microglial cell as macrophage in the brain. Methods: First, we tested the CRH receptor expression in the mRNA levels by RT-PCR. To test the regulation of NO release by CRH, cells were treated with CRH and then NO release was measured by Griess reagent assay. Results: Our study demonstrated that CRH receptor 1 was expressed in BV2 murine microglial cells and CRH treatment enhanced NO production. Furthermore, additive effects of lipopolysaccaride (LPS) and CRH were confirmed in NO production time dependantly. Conclusion: Taken together, these data indicated that CRH is an important mediator to regulate NO release on microglial cells in the brain during stress.

• 전자공학회논문지SC
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• 제48권2호
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• pp.80-85
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• 2011

알츠하이머병(AD: Alzheimer's disease)과 파킨슨병(PD: Parkinson's disease)은 가장 흔한 퇴행성 뇌신경질환이다. 본 연구에서는 라만 스펙트럼을 이용하여 AD와 PD를 분류하기 위해 특징 추출하는 방법을 제안하였다. 혈소판으로부터 측정한 라만 스펙트럼에 먼저 smoothing을 적용한 다음 기준선의 왜곡을 제거하고 스펙트럼의 기준 피크를 중심으로 그 위치를 정렬하는 순서로 이루어진 전처리 과정을 적용하였다. 전처리 과정을 수행한 스펙트럼에서 AD와 PD를 구별할 수 있는 특징을 조사하였고 그 결과 743과 $757cm^{-1}$ 영역의 피크 비와 1248과 $1448cm^{-1}$ 영역의 피크 크기가 가장 변별력 있는 특징임을 확인하였다. 실험 결과에 따르면, 총 216개의 라만 스펙트럼에 대한 MAP(maximum a posteriori probability) 분류 실험에서 이 세 개의 특징만으로도 약 95.8%의 분류율을 보였다.

• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.494-496
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• 2018

No previous reports have described a case in which deep brain stimulation elicited an acute mood swing from a depressive to manic state simply by switching one side of the bilateral deep brain stimulation electrode on and off. The patient was a 68-year-old woman with a 10-year history of Parkinson's disease. She underwent bilateral subthalamic deep brain stimulation surgery. After undergoing surgery, the patient exhibited hyperthymia. She was scheduled for admission. On the first day of admission, it was clear that resting tremors in the right limbs had relapsed and her hyperthymia had reverted to depression. It was discovered that the left-side electrode of the deep brain stimulation device was found to be accidentally turned off. As soon as the electrode was turned on, motor impairment improved and her mood switched from depression to mania. The authors speculate that the lateral balance of stimulation plays an important role in mood regulation. The current report provides an intriguing insight into possible mechanisms of mood swing in mood disorders.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.127-134
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• 2021

Neuroinflammation―a common pathological feature of neurodegenerative disorders such as Alzheimer's disease―is mediated by microglial activation. Thus, inhibiting microglial activation is vital for treating various neurological disorders. 7,3',4'-Trihydroxyisoflavone (THIF)―a secondary metabolite of the soybean compound daidzein―possesses antioxidant and anticancer properties. However, the effects of 7,3',4'-THIF on microglial activation have not been explored. In this study, antineuroinflammatory effects of 7,3',4'-THIF in lipopolysaccharide (LPS)-stimulated BV2 microglial cells were examined. 7,3',4'-THIF significantly suppressed the production of the proinflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) as well as of the proinflammatory cytokine interleukin-6 (IL-6) in LPS-stimulated BV2 microglial cells. Moreover, 7,3',4'-THIF markedly inhibited reactive oxygen species (ROS) generation. Western blotting revealed that 7,3',4'-THIF diminished LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), and nuclear factor kappa B (NF-κB). Overall, 7,3',4'-THIF exerts antineuroinflammatory effects against LPS-induced microglial activation by suppressing mitogen-activated protein kinase (MAPK) and NF-κB signaling, ultimately reducing proinflammatory responses. Therefore, these antineuroinflammatory effects of 7,3',4'-THIF suggest its potential as a therapeutic agent for neurodegenerative disorders.

• Journal of Ginseng Research
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• 제31권3호
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• pp.117-126
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• 2007

Ginseng, the root of Panax species, a well-known herbal medicine has been used as a traditional medicine for thousands of years and is now a popular and worldwide used natural medicine. Ginseng has been used primarily as a tonic to invigorate weak bodies to help the restoration of homeostasis in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency and hepatotoxicity. Although conclusive clinical data in humans is still missing, recent research results have suggested that some of the active ingredients ginseng exert beneficial effects on central nervous system (CNS) disorders and neurodegenerative diseases, suggesting it could be used in treatment of psychotic disorders. Data from neural cell cultures and animal studies contribute to the understanding of these mechanisms that involve inhibitory effects on stress-induced corticosterone level increasing and modulating of neurontransmitters, reducing $Ca^{2+}$ over-influx, scavenging of free radicals and counteracting excitotoxicity. In this review, we focused on recently reported medicinal effects of ginseng and summarized the possibility of its applications on psychotic disorders.

• Nuclear Medicine and Molecular Imaging
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• 제42권sup1호
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• pp.166-171
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• 2008

PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. $^{18}F-FDG$ PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, $^{18}F-FDG$ PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers $^{18}F-FDG$ PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of $^{18}F-FDG$ PET in the diagnosis or treatment of dementing neurodegenerative diseases.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1999년도 춘계학술대회
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• pp.1-4
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• 1999

The potential therapeutic benefit of nicotinic ligands in a variety of neurodegenerative pathologies involving the CNS has energized research efforts to develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands. In particular, there has been a concerted effort to develop nicotinic compounds with selectivity for CNS nAChRs as potential pharmacological tools in the management of these disorders. The characterization of other novel nicotinic ligands such as epibatidine. showing a marked increase in potency at nAChRs, has provided additional support for the development of potent, selective ligands at individual nAChR subtypes. We have developed and studied a number of nicotinic compounds to identify potential candidates exhibiting such selectivity. In the present study, we report the synthesis and biological evaluations of some azabicyclic and azatricyclic nicotine analogs to decipher the relationship among steric requirements of the nicotine's pyrrolidine ring system, binding affinity and subtype-selectivity.

• 분석과학
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• 제30권6호
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• pp.355-378
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• 2017

신경전달물질(neurochemicals)은 인체 내의 항상성유지와 인지 및 행동기능에 관여하므로 수많은 퇴행성신경질환 진단에 활용할 수 있어 생물학적 시료 내에서 신경화학물질을 프로파일링할 수 있는 분석플랫폼 개발에 대한 관심이 증가하고 있다. 특히, 크로마토그래피 분리법과 결합된 질량분석법 기반의 분석법은 대사경로 내의 신경전달물질을 프로파일링하는 데 널리 사용되어 오고 있다. 하지만 생물학적 시료내 신경전달물질은 극미량으로 존재하며 화학적으로 불안정한 특징이 있어 정교한 시료전처리 과정과 고감도의 기기분석법의 개발이 수반되어야 한다. 따라서 본 총설 논문에서는 소변, 혈액, 뇌척수액과 생체조직과 같은 다양한 생물학적 시료에서 신경전달물질에 대한 질량분석법 기반의 대사체학 접근법의 분석 연구 경향에 대해서 논의할 예정이다. 이 논문은 향후 퇴행성신경질환의 진단, 예후예측과 치료를 가능하게 하는 생체지표물질을 발굴을 위한 분석플랫폼 개발에 기여할 것으로 기대된다.

• 생물정신의학
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• 제23권2호
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• pp.48-56
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• 2016

Alzheimer's disease (AD) is a neurodegenerative disorder in which neuronal loss causes cognitive decline and other neuropsychiatric problems. It can be diagnosed based on history, examination, and appropriate objective assessments, using standard criteria such as the Diagnostic and Statistical Manual of Mental Disorders or the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Brain imaging and biomarkers are making progress in the differential diagnoses among the different disorders. The cholinesterase inhibitors, donepezil, rivastigmine and galantamine and N-methyl-D-aspartate receptors antagonist memantine are approved by the US Food and Drug Administration for AD. Recently some acetylcholinesterase inhibitors gained approval for the treatment of severe AD and became available in a higher dose formulation or a patch formulation. Optimal care in AD is multifactorial and it should include early diagnosis and multidisciplinary care with pharmacological and nonpharmacological interventions including exercise interventions, cognitive interventions and maintenance of social networks.