• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.643-650
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• 2017

Vascular dementia (VaD) is a group of heterogeneous diseases with the common feature of cerebral hypoperfusion. To identify key factors contributing to VaD pathophysiology, we performed a detailed comparison of Wistar and Sprague-Dawley (SD) rats subjected to permanent bilateral common carotid artery occlusion (BCCAo). Eight-week old male Wistar and SD rats underwent BCCAo, followed by a reference memory test using a five-radial arm maze with tactile cues. Continuous monitoring of cerebral blood flow (CBF) was performed with a laser Doppler perfusion imaging (LDPI) system. A separate cohort of animals was sacrificed for evaluation of the brain vasculature and white matter damage after BCCAo. We found reference memory impairment in Wistar rats, but not in SD rats. Moreover, our LDPI system revealed that Wistar rats had significant hypoperfusion in the brain region supplied by the posterior cerebral artery (PCA). Furthermore, Wistar rats showed more profound CBF reduction in the forebrain region than did SD rats. Post-mortem analysis of brain vasculature demonstrated greater PCA plasticity at all time points after BCCAo in Wistar rats. Finally, we confirmed white matter rarefaction that was only observed in Wistar rats. Our studies show a comprehensive and dynamic CBF status after BCCAo in Wistar rats in addition to severe PCA dolichoectasia, which correlated well with white matter lesion and memory decline.

• Journal of Acupuncture Research
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• v.18 no.2
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• pp.67-78
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• 2001

The aim of this study was to examine the effects of low frequency electroacupuncture(EA) at the $B_{62}$ (Shinmaek) $K_6$(Chohae) on vascular dementia in humans using nonlinear dynamics. Electroencephalogram(EEG) is a multi-scaled signal consisting of several components of time series with different dominant frequency ranges and different origins. Nonlinear measures of the EEG like the correlation dimension ($D_2$) and the first positive Lyapunov exponent ($L_1$) reflect the complexity of the EEG. In this study, $D_2$ was used as a measure of complexity. Sixteen channel EEG study was carried out in six subjects (5 females and 1 males; $age=83.83{\pm}7.19years$). We found that the baseline $D_2$ values of the EEG at F4 and F8 channels (P<0.01) were lowered than during the acupuncture treatment, indicating decreased complexity of the EEG. However, the comparison with that before and after the treatment shows no significant differences in all channels.

• Vascular Specialist International
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• v.34 no.4
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• pp.109-116
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• 2018

Purpose: Diabetic foot wound (DFW) is known as a major contributor of nontraumatic lower extremity amputation. We aimed to evaluate overall amputation rates and risk factors for amputation in patients with DFW. Materials and Methods: From January 2014 to December 2017, 141 patients with DFW were enrolled. We determined rates and risk factors of major amputation in DFW and in DFW with peripheral arterial occlusive disease (PAOD). In addition, we investigated rates and predictors for amputation in diabetic foot ulcer (DFU). Results: The overall rate of major amputation was 26.2% in patients with DFW. Among 141 DFWs, 76 patients (53.9%) had PAOD and 29 patients (38.2%) of 76 DFWs with PAOD underwent major amputation. Wound state according to Wagner classification, congestive heart failure, leukocytosis, dementia, and PAOD were the significant risk factors for major amputation. In DFW with PAOD, Wagner classification grades and leukocytosis were the predictors for major amputation. In addition, amputation was performed for 28 patients (38.4%) while major amputation was performed for 5 patients (6.8%) of 73 DFUs. Only the presence of osteomyelitis (OM) showed significant difference for amputation in DFU. Conclusion: This study represented that approximately a quarter of DFWs underwent major amputation. Moreover, over half of DFW patients had PAOD and about 38.2% of them underwent major amputation. Wound state and PAOD was major predictors for major amputation in DFW. Systemic factors, such as CHF, leukocytosis, and dementia were identified as risk factors for major amputation. In terms of DFU, 38.4% underwent amputation and the presence of OM was a determinant for amputation.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.83-90
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• 2012

Objectives : Modified Bo-Yang-Hwan-O-Tang (mBHT) is a polyherbal medicine of twelve herbs traditionally used in the treatment of cerebral and cardiac stroke and vascular dementia. The purpose of this study was to evaluate the neuroprotective effect, pyramidal neuronal cell, inflammation and apoptosis of mBHT against global ischemia in rats. Methods : Global ischemia was produced by two-vessel occlusion(2-VO) in SD male rats. mBHT at dose of 500 mg/kg was orally administrated for 2 weeks or 6 weeks after global ischemia. The histopathological changes of ischemic brain were observed by staining of hematoxylin and eosin (H&E) and Nissl and immunohistochemisty with anti-GFAP (glial fibrillary acidic protein) antibody as a astrocyte marker. The expression of inducible nitric oxide synthase (iNOS) and apoptotic proteins such as Bax, Bcl-2 and caspase-3 was determined by western blot. Results : mBHT treatment significantly inhibited the pyramidal neuronal loss in CA1 of hippocampus of global ischemic rats by 2-VO. mBHT also suppressed the activation of astrocytes in the CA1 at 6 weeks after ischemia. In addition, mBHT significantly increased the expression of anti-apoptotic protein, Bcl-2 on iscemic brain, and significantly attenuated the expression of apoptotic proteins, Bax and caspase-3. Conclusions : These results indicate that mBHT inhibits neuronal cell damage induced in global ischemia by 2-VO, suggesting that mBHT may be a potential candidate for the treatment of vascular dementia.

• Journal of Oriental Neuropsychiatry
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• v.16 no.2
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• pp.73-88
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• 2005

Object : This study was designed to asses the effect of Kunnuetang and herbs on Mouse neuroblastoma 2a cells damaged by hypoxia-reoxygenation. Method : Mouse neuroblastoma 2a (N2a) cells were measured by MTT assay and LDH assay after 48h hypoxia and 6h reoxygenation. Mouse neuroblastoma 2a (N2a) cells were treated by Kunnuetang, Duchang and Daejo. Result : 1. Kunnuetang, was effective on LDH assay of hypoxia and reoxygenation. 2. Duchang and Daejo were generally effective on LDH assay of hypoxia and reoxygenation. 3. In MTT assay of hypoxia Kunnuetang was not effective. Duchung and Daejo were not generally effective on MTT assay, but in certain condition Herbs were effective. 4. In MTT assay of reoxygenation Kunnuetang and Daejo were not effective. But Duchung was effective in certain condition. Conclusion : The results suggest that Kunnuetang, Duchang and Daejo may have protective effect on vascular dementia and ad patient.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.374-380
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• 2000

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be a compound for treatment of both vascular dementia and dementia of the Alzheimer type. The short half-life (about 15 min) of PPF at the terminal elimination phase and poor bioavailability after oral administration of PPF to rabbits (Kim et al., 1992) suggest in part that this drug takes the extensive first-pass metabolism in the liver. In addition, the metabolic pathway for PPF remains unclear. The objective of this experiment is to identify urinary metabolites of PPF in rats. For the identification of the metabolites, rat urine was collected after oral administration of 100${m}g/kg$ PPF. PPF metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine, was synthesized and confirmed by gas chromatography/mass spectroscopy (GC/MS) and $^1H$ nuclear magnetic resonance spectroscopy. The urinary metabolites of PPF were extracted with diethyl ether and identified by electron impact and chemical ionization GC/MS. One urinary metabolite was confirmed to be 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine by synthesized authentic compound. Several metabolites of monohydroxy- and dihydroxy-PPF were identified based on mass fragmentation of both intact and trimethylsilylated derivatives of PPF metabolites and the novel structure of these metabolites is suggested based on mass spectra.

• Dementia and Neurocognitive Disorders
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• v.22 no.3
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• pp.87-99
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• 2023

Background and Purpose: According to the amyloid cascade hypothesis, fibrillary amyloid-beta load in the brain causes Alzheimer's disease (AD) with toxic effects. Recently, perivascular spaces (PVSs), fluid-filled cavities around small penetrating arterioles and venules in the brain, and the glymphatic system relationship with type 2 diabetes mellitus (DM2) and AD has been an important research topic from a physiopathological point of view. There are two types of PVSs that are associated with sporadic atherosclerosis and cerebral amyloid angiopathy. In this study, we evaluated the relationship between the number and localization of enlarged PVSs in AD. Methods: A total of 254 patients with AD and 125 healthy controls were included in this study All the patients were evaluated with neurological and cognitive examinations and magnetic resonance imaging (MRI). PVSs on MRI were graded by recording their number and location. The study was a retrospective study. Results: In our study, the number of white matter convexity-central semiovale localized PVSs was higher in patients than in the control group. In addition, the number of PVSs in this localization score was higher in patients with DM2. Cerebral PVS counts were higher in patients with AD than in the control group. Conclusions: These results suggest the important role of cerebral amyloid angiopathy, one of the vascular risk factors, and the glymphatic system in the pathogenesis of AD. In addition, the results of our study suggest that the evaluation of PVSs levels, especially at the (centrum semiovale), using imaging studies in AD is a potential diagnostic option.

• The Journal of Internal Korean Medicine
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• v.38 no.5
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• pp.628-640
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• 2017

Purpose: To describe the effectiveness of traditional Korean medicine (TKM) on the patients with secondary dementia (case 1: Rt. MCA infarction; case 2: traumatic subacute subdural hemorrhage and traumatic intracranial hemorrhage; case 3: delayed encephalopathy after carbon monoxide poisoning). Methods: We used a complete TKM treatment. The acupoints used were as follows: acupoints frequently used in hemiparesis (GV20, GV24, ST4, LI11, LI14, ST36, GB34, SP9, and LR3), and we used herbal medicine (補腎益腦湯加味, Boshiniknoe-tang-gami). The efficacy was evaluated using the Mini-Mental State Examination for Dementia Screening (MMSE-DS) and the Modified Barthel Index (MBI). Results: After treatment, the total MMSE-DS score was increased from 14 to 24 (case 1), 14 to 19 (case 2), and 0 to 17 (case 3). The total K-MBI was increased from 30 to 44 (case 1), 82 to 86 (case 2), and 30 to 86 (case 3) Conclusions: We suggest that TKM could positively influence cognition and improve activity of daily living (ADL). This study has limitations, so further studies are needed.

• Journal of Yeungnam Medical Science
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• v.36 no.3
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• pp.183-191
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• 2019

Some patients with type 1 and type 2 diabetes mellitus (DM) present with cognitive dysfunctions. The pathophysiology underlying this complication is not well understood. Type 1 DM has been associated with a decrease in the speed of information processing, psychomotor efficiency, attention, mental flexibility, and visual perception. Longitudinal epidemiological studies of type 1 DM have indicated that chronic hyperglycemia and microvascular disease, rather than repeated severe hypoglycemia, are associated with the pathogenesis of DM-related cognitive dysfunction. However, severe hypoglycemic episodes may contribute to cognitive dysfunction in high-risk patients with DM. Type 2 DM has been associated with memory deficits, decreased psychomotor speed, and reduced frontal lobe/executive function. In type 2 DM, chronic hyperglycemia, long duration of DM, presence of vascular risk factors (e.g., hypertension and obesity), and microvascular and macrovascular complications are associated with the increased risk of developing cognitive dysfunction. The pathophysiology of cognitive dysfunction in individuals with DM include the following: (1) role of hyperglycemia, (2) role of vascular disease, (3) role of hypoglycemia, and (4) role of insulin resistance and amyloid. Recently, some investigators have proposed that type 3 DM is correlated to sporadic Alzheimer's disease. The molecular and biochemical consequences of insulin and insulin-like growth factor resistance in the brain compromise neuronal survival, energy production, gene expression, plasticity, and white matter integrity. If patients claim that their performance is worsening or if they ask about the effects of DM on functioning, screening and assessment are recommended.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.6
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• pp.530-537
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• 2007

Purpose: The aim of this study is to assess the specific patterns of regional cerebral blood flow (rCBF) in patients with the early stage of subcortical vascular dementia (SVaD) and Alzheimer's disease (AD) using Tc-99m HMPAO SPECT, and to compare the differences between the two conditions. Materials and Methods: Sixteen SVaD, 46 AD and 12 control subjects participated in this study. We included the patients with SVaD and AD according to NINCDS-ADRDA and NINDS-AIREN criteria. They were all matched for age, education and clinical dementia rating scores. Three groups were evaluated by Tc-99m HMPAO SPECT using statistical parametric mapping (SPM) for measuring rCBF. The SPECT data of patients with SVaD and AD were compared with those of normal control subjects and then compared with each other. Results: SPM analysis of the SPECT image showed significant perfusion deficits on the right temporal region and thalamus, left insula and superior temporal gyrus, both cingulate gyri and frontal subgyri in patients with SVaD and on the left supramarginal gyrus, superior temporal gyrus, postcentral gyrus and inferior parietal lobule, right fugiform gyrus and both cingulate gyri in AD compared with control subjects (uncorrected p<0.01). SVaD patients revealed significant hypoperfusion in the right parahippocampal gyrus with cingulated gyrus, left insula and both frontal subgyral regions compared with AD (uncorrected p<0.01). Conclusion: Our study shows characteristic and different pattern of perfusion deficits in patients with SVaD and AD, and these results may be helpful to discriminate the two conditions in the early stage of illness.