• Journal of the Optical Society of Korea
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• v.20 no.1
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• pp.88-93
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• 2016

Recently laser speckle contrast (LSC) imaging has become a widely used optical method for in vivo assessment of blood flow in the animal brain. LSC imaging is useful for monitoring brain hemodynamics with relatively high spatio-temporal resolution. A speckle contrast imaging system has been implemented with electrical sensory stimulation apparatus. LSC imaging is combined with optical intrinsic signal imaging in order to measure changes in cerebral blood flow as well as neural activity in response to electrical sensory stimulation applied to the hindlimb region of the mouse brain. We found that blood flow and oxygen consumption are correlated and both sides of hindlimb activation regions are symmetrically located. This apparatus could be used to monitor spatial or temporal responses of cerebral blood flow in animal disease models such as ischemic stroke or cortical spreading depression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.3
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• pp.645-661
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• 2009

The water extract of Dohongsamul-Tang(DHSMT) has been traditionally used to stroke and brain injuries in Oriental Medicine. The present study was designed to investigate the effects of DHSMT on the gene expression profile of cerebral infarction by cDNA microarray in photothrombotic ischemia mouse model. Photothrombotic ischemia was induced in stereotactically held male BALB/c mice using rose bengal and cold light. MRI was performed 24 hours after inducing photothrombosis using 1.5 T MRI and 47 mm surface coil to obtain T2-weighted, and contrast-enhanced images. After MRI test, animal was sacrificed and the brain sections were stained for hematoxylin and eosin and immunohistochemistry. MRI and histological analysis revealed that lesion of thrombotic ischemia was well induced in the cortex with the evidence of biological courses of infarction. The target area of thrombotic infarction was 1 mm anterior to bregma and 3 mm lateral to midline with 2 mm in diameter, which were decreased by administration of DHSMT. To assess gene expression pattern of cerebral infarction, mRNA was isolated and reacted with microarray chip(Agilant's DNA Microarray 44K). Scatter and MA plot analysis were performed to clustering of each functional genes. M value [M=log2(R/G), A={log2(R ${\times}$ G)}/2] was between -0.5 and +0.5 with 40% difference. After pretreatment with DHSMT, the expression levels of mRNA of many genes involved in various signaling pathway such as apoptosis, cell cycle, cell proliferation, response to oxidative stress, immune response, angiogenesis, and inflammatory cytokine were markedly inhibited in photothrombotic ischemia lesion compared to the control group. These results suggest that DHSMT prevent ischemic death of brain on photothrombotic ischemia model of mice through modulation of gene expression at the transcriptional level.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.3
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• pp.164-176
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• 2016

This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.

• Journal of Oriental Neuropsychiatry
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• v.24 no.1
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• pp.123-130
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• 2013

Objectives : During several thousand years, Peucedanum Japonicum Thunberg has been considered as a vegetable side dish in Korea. There is folk knowledge that Peucedanum Japonicum Thunberg prevents vascular disease such as stroke. To identify the effects Peucedanum Japonicum Thunberg, we made up its extract and named it as KH020. Then, we employed common carotid artery ligation (CCAl) surgery for vascular dementia model (VDM), and two types doses of per os (per oral: p.o) treatment. Methods : To confirm prevention and recovery effects for vascular dementia, we treated two doses (100, 400 mg/kg) KH020 in male C57BL/6 mouse during 7 days. After treatment, animals were CCAl operated, and given time to recover. Then, animal were tested in a Y-maze and passive avoidance test. Results : Y-maze results demonstrated that cognition and memory performance were decreased in the VDM group, compared to the sham group. KH020 treatment abolished these effects significantly. The results from the passive avoidance test showed the same phenomenon, but it was not statically significant. Conclusions : Therefore, KH020 prevents the onset of vascular dementia. In future studies, we will evaluate KH020 in regard to alzheimer dementia.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.65-71
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• 2003

Increasing evidences suggest that ischemia-induced vascular damage is an integral step in the cascade of the cellular and molecular events initiated by cerebral ischemia. In the present study, employing a mouse brain endothelioma-derived cell line, bEnd.3, and oxygen-glucose deprivation (OGD) as an in vitro stroke model, the role of nuclear factor kappa B (NF-${\kappa}B$) activation during ischemic injury was investigated. OGD was found to activate NF-${\kappa}B$ and to induce bEnd.3 cell death in a time-dependent manner. OGD phosphorylated neither 32 Ser nor 42 Tyr of $I{\kappa}B{\alpha}$. OGD did not change the amount of $I{\kappa}B{\alpha}$. The extents of OGD-induced cell death after 8 h, 10 h, 12 h and 14 h of OGD were 10%, 35%, 60% and 85%, respectively. Reperfusion following OGD did not cause additional cell death, indicating no reperfusion injury after ischemic insult in cerebral endothelial cells. Three known as NF-${\kappa}B$ inhibitors, including pyrrolidine dithiocarbamate (PDTC) plus zinc, aspirin and caffeic acid phenethyl ester (CAPE), inhibited OGD-induced NF-${\kappa}B$ activation and increased OGD-induced bEnd.3 cell death in a dose dependent manner. There were no changes in the protein levels of bcl-2, bax and p53 which are modulated by NF-${\kappa}B$ activity. These results suggest that NF-${\kappa}B$ activation might be a protective mechanism for OGD-induced cell death in bEnd.3.

• Journal of the Ergonomics Society of Korea
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• v.34 no.4
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• pp.335-351
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• 2015

Objective: The aim of this study was to perform a usability test for CPAD (Cognitive Perceptual Assessment for Driving) and improve it based on the test results. Background: The cognitive perceptual assessment for driving is a computer-based assessment tool to assess the driving capacity of people with brain-damages. It may be a good tool for evaluating the brain-damaged drivers' safe driving capabilities and screening cognitive and perceptual deficits related to driving. We performed a usability test to improve the CPAD based on the result. Method: Both the software consisting of 8 sub-tests (depth perception, sustained attention, divided attention, stroop test, field dependency, digit span, trail making A, trail making B) and the hardware including the input and output devices ( joystick, mouse, keyboard, touch screen) were evaluated through user interviews. Also we identified the problems and issues in using them by observing the participants performing the CPAD tasks. Results: Based on the results, the task instructions were visually and auditorily improved and more practice examples were added to help the users understand the instructions better and increase the input accuracy, a response time window was added and the joystick and touch screen were simplified, which made it easier for the user to perform the CAPD tasks. Conclusion: User discomforts were minimized by improving the task environment, unless it had affected the evaluation criteria. Application: We plan to distribute the improved version of the CPAD to the regional rehabilitation hospitals, and the driving support centers for people with disabilities throughout the country, so it could be used as an evaluation tool for disabled drivers' cognitive and perceptual functions.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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• pp.139-149
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• 2006

Amyloid beta (A$\beta$) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of A$\beta$ is considered a primary therapeutic target. Immunization with A$\beta$ can reduce A$\beta$ burden and pathological features in transgenic AD model mouse. This means anti-A$\beta$ autoantibodies may have a role in AD pathology. Recent findings suggest anti-A$\beta$ autoantibodies level decrease in AD patients. The early detection of AD is important for treatment of this disease. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. To investigate whether it was possible to detect the presence and different levels of naturally occurring anti-A$\beta$ autoantibodies in the plasma of patients with AD and age-matched controls. An advanced ELISA was performed to detect levels of naturally occurring anti-A$\beta$ autoantibodies in the plasma. The level of anti-A$\beta$ auto-antibodies from patients with idiopathic Parkinson's disease or stroke and from normal controls were compared to that of AD patients. Our results showed a significantly lower anti-A$\beta$ autoantibodies level in AD compared to those with other neurological diseases or control. The level of anti-A$\beta$ autoantibodies in the serum may be used to diagnose the presence of AD.

• 한국약용작물학회:학술대회논문집
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• 2006.04a
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• pp.137-149
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• 2006

Amyloid beta ($A{\beta}$) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of $A{\beta}$ is considered a primary therapeutic target. Immunization with $A{\beta}$ can reduce $A{\beta}$ burden and pathological features in transgenic AD model mouse. This means $anti-A{\beta}$ autoantibodies may have a role in AD pathology. Recent findings suggest $anti-A{\beta}$ autoantibodies level decrease in AD patients. The early detection of AD is important for treatment of this disease. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. To investigate whether it was possible to detect the presence and different levels of naturally occurring $anti-A{\beta}$ autoantibodies in the plasma of patients with AD and age-matched controls. An advanced ELISA was performed to detect levels of naturally occurring $anti-A{\beta}$ autoantibodies in the plasma. The level of $anti-A{\beta}$ auto-antibodies from patients with idiopathic Parkinson's disease or stroke and from normal controls were compared to that of AD patients. Our results showed a significantly lower $anti-A{\beta}$ autoantibodies level in AD compared to those with other neurological diseases or control. The level of $anti-A{\beta}$ autoantibodies in the serum may be used to diagnose the presence of AD.

• Journal of Acupuncture Research
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• v.30 no.3
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• pp.1-13
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• 2013

Objectives : This study was performed to choose more effective neuro-protective acupuncture point and to verify the effect of acupuncture in promoting neurogenesis and angiogenesis as a result of its neuro-vasculo-regenerative effect in middle cerebral artery occlusion model in rats. Methods : By TTc staining we chose the most effective acupuncture point with neuro-protection. We randomly divided into four groups: Such as (1) sham group(with sham-operation), (2) sham+acupuncture group(with sham-operation), (3) middle cerebral artery occlusion group, (4) MCAO+AT group. Acupuncture procedure was performed for four days. Total RNA was extracted using TRIzol reagent, according to the manufacturer's instructions, and was purified using an RNAeasy mini kit. Immuno-histochemistry was performed using primary antibody mouse anti-BrdU, NeuN, Dcx, and VEGF. Results : We found that $ST_{36}$ had the more neuroprotective effect than $LI_{11}$ and $SP_3$. The microarray analysis revealed that 54 genes were more expressed neurogenesis pathway in MCAO+AT group compared with MCAO group(fold changes greater than or equal to twofold change). 11 genes were more expressed angiogenesis pathway. And 7 genes were more expressed VEGF pathway. Immuno-histochemistry revealed that cell proliferation, cell migration and cell maturation were increased. Conclusions : This study demonstrated that acupuncture on $ST_{36}$ had neuro-protective and neuro-restorative effect in ischemic brain injuries. And its mechanism might be related to promote neurogenesis and angiogenesis. These results suggest that acupuncture have potential benefits for the treatment of ischemic stroke.

• Molecules and Cells
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• v.45 no.4
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• pp.216-230
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• 2022

SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.