• Journal of Chest Surgery
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• 제31권10호
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• pp.945-951
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• 1998

개심술시 총순환정지는 매우 유용한 방법이나 뇌손상등 부작용으로 그 사용이 제한되고 있다. 이러한 뇌손상의 분석에 유용한 지표로서 뇌 허혈성 손상의 특이한 효소인 크레아티닌 카이네이즈 BB(CK-BB)의 유용성을 재고하고 뇌손상에 영향을 미치는 인자들의 분석을 시도하였다. 총순환정지를 이용하여 개심술을 시행한 18명의 환자를 대상으로 하였다. 이들은 다시 비청색증형 심기 형군과 청색증형 심기형군으로 나누어 각각 6명과 12명으로 하였다. 각 환자에서 총순환정지전 및 후 15, 30, 60, 120, 240, 480, 720분에 동맥혈을 채취하여 CK-BB분획을 측정하였고 이와 동시에 혈색소농도, 이 온화 칼슘농도, 혈당량 등을 측정하였다. 총순환정지시간과 CK-BB와 통계적으로 유의한 관계를 보이는 채혈시간은 찾을 수 없었다. 또 총순환 정지전의 문제로 인한 영향을 줄이기 위하여 각각의 측정치에서 총순환정지전의 측정치를 뺀 값을 구하 여 각기 CKBBD15, CKBBD30....등으로 표시하고 상관관계를 구하였으나 역시 유의한 상관관계를 보이 지 않았다. CKBB30과 CKBBD30값은 비청색증형 군과 청색증형 군 사이에 유의한 차이를 보이지 않았 다. CK-BB농도와 혈색소 농도는 유의한 상관관계를 보였다. 단일 채혈에 의한 CK-BB농도의 지표는 순환정지시간과 유의한 관계가 없음이 확인되었다. 또한 청색 증형 심질환군이 총순환정지에 의한 뇌손상에 비청색증형 심질환군에 비해 더 취약하지는 않은 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제15권1호
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제21권5호
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• pp.475-485
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• 2017

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7-36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7-36) (10, 20, $40{\mu}g/kg$ i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7-36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7-36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7-36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.

• Journal of Chest Surgery
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• 제41권6호
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• pp.718-723
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• 2008

배경: 최근 20년간 수술적인 기법, 마취 기술, 심폐기 운용, 중환자실 관리의 발전으로 심장수술의 사망률과 합병증은 상당히 감소하였지만 심장수술이 중추신경계에 상당한 위험 요소가 되는 것은 널리 알려진 바이다. 이 연구는 두경부 MRA를 통해 심장 수술 대상자에서 불현성 뇌혈관계 질환의 유병률과 두경부 MRA 상에서 비정상적인 소견을 보인 환자의 치료 방침의 변화를 알아보고자 하였다. 대상 및 방법: 2005년 10월부터 2008년 6월까지 두경부 MRA 촬영에 동의한 107명의 심장수술 예정자(21세에서 83세까지의 연령분포를 보인 남자 71명과 여자 36명)를 대상으로 하였다. 이 환자들 중에서 신경학적인 고위험군의 비율과 그 환자들의 치료 방침의 변화를 관찰하였다. 결과: 신경학적으로 고위험군 환자의 비율은 15.7% (17예)였으며, 이중 11예는 허혈성 심질환, 6예는 판막 질환이였으며, 이 중 2예의 환자만이 이전에 신경학적인 병력이 있었다. 14명(13.1%)의 환자에서 치료 방침에 변화가 있었다. 결론: 심장수술 대상자에 있어 불현성 뇌혈관계 질환은 비교적 높은 것으로 생각되며, 이를 밝히는 데 있어 두경부 MRA가 의미 있는 것으로 생각된다.

• 대한한방내과학회지
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• 제21권1호
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• pp.116-125
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• 2000

Objectives : The aim of this study is to investigate that Sunghyangjeongki-San which has been frequently medicated in the early stage of stroke can protect against ischemic damage in rat brain Methods : Extracellular levels of amino acids(glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine), organic acids(pyruvate, lactate), and cerebral infarction volume were measured at the striatum of rats subjected to permanant focal cerebral ischemia induced by 2 hours of middle cerebral artery occiusion(MCAO). Rats were orally administered with Sunghyangjeongki-San at 30mins before MCAO and the microdialysate was collected by intracerebral microdialysis three times before MCAO and six times after MCAO at 20mins interval and analyzed by HPLC. After a microdialysis study, the brain was sliced and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume by image analyzer system Results : The concentrations of glutamate, aspartate, and tyrosine known as excitatory neurotransmitters were significantly decreased in Sunghyangjeongki-San group compared with control group, The concentrations of GABA, glycine, taurine and alanine known as inhibitory neurotransmitters were significantly increased in Sunghyangjeongki-San group compared with control group. The concentrations of pyruvate and lactate showed little significant change in Sunghyangjeongki-San group compared with control group. The measurement of cerebral infarcted area and volume by image analyzer system were significantly decreased in Sunghyangjeongki-San group compared with control group. Conclusions : Sunghyangjeongki-San can affect on protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters and improve the conditions of the patients in the early stage of stroke.

• 대한한방내과학회지
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• 제19권1호
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• pp.301-317
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• 1998

A clinical analysis was carried out for 32 patients who were treated in Dept. of Dong-shin Oriental Medicine Hospital from 10st January to 16st May in 1998 and ruled out as dememtia. The results were summarized as follows. 1. In the distribution of sex, female was more than male. And the age of seventies(17 cases, 53.125%) was highest in the frequency of age. 2. In the distribution of having history of drinking and smoking were each 4 cases(12.5%) and 7 cases(21.875%). 3. In the distribution of seasons, the ratio of spring and winter were each 16 cases(50.0%), 15 cases(46.875%), that of summer and fall were comparatively low. 4. In the period from onset to admission, the period within a week had 20 cases(62.5%) as top, and the most period of treatment was 2 and 3 weeks(28.125%). 5. The number of cases that had preceding disease was 35 cases(71.875%), a major portion of preceding diseases were hypertension, diabetes mellitus, stroke. 6. The most common symptom was disorientation(78.125%), and the next common symptom was motor desability(71.875%), and memory disturbance, verbal disturbance was each 59.375 and 47.1%. 7. In the distribution of the CT scan films, 15 cases(46.875%) showed cerebral infarction and that of another 5cases (15.625%) showed cerebral hemorrhage, that of another 2 cases(6.25%) showed brain atrophy. 8. In the lipid density of blood, T-Cholesterol, TG, HDL-Cholesterol, LDL- Cholesterol was within normal limit. 9. In the MMSE-K, the most score was from 16 point to 20 point, and second only was from 11 point to 15 point, and the next was from 6 point to 10 point. 10. In the Ischemic score, 20 cases(62.5%) was diagnosed as brain vascular type dementia, and mixed type dementia was 9 cases(28.125%), Alzheimer type dementia was 3 cases(9.375%). 11. The most used recipes were a sort of recipes to activate of flow the vital energy and the blood, to remove the phlegm(41 cases 33.9%), especially DODAMHOALHEL TANG (12 cases, 9.9%), ANSINCHUNGNOITANG (8 case, 6.6%) was the most used recipe. 12. In the judgement of efficacy, 17 cases(53.125%) showed excellent efficacy, 10 cases(31.25%) showed good efficacy, 5 cases(15.625%) showed no change and that according to MMSE-K, 4 case(18.18%) showed excellent efficacy, 15 cases(68.18%) showed good efficacy, 15 cases(68.18%) showed no change.

• 동의신경정신과학회지
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• 제21권1호
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• pp.59-69
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• 2010

Objectives: The study aims to look into how the application of EA(Electro-acupuncture) in the initial step of ischemic brain injury affects the changes in Bax and Caspase-3 expression among forebrain apoptosis. Methods: It caused GI by using common carotid artery occlusion and conducted the test by dividing into the no applied EA group after 6 hours and 12 hours, the LI 4 EA group that applied EA to LI4, and GV 20 EA group that was applied to GV 20. After that, the following results were obtained by comparing Bax and Caspase-3 expression, which were apoptosis-related factors, with its application time through immunohistochemical staining after extracting brain of each group. Results: According to each group's Bax expression by the application time, the order of expression increase after 6 hours is shown to be the no applied EA group, LI 4 group, and GV 20 group. The stimulation after 12 hours was most lowly expressed in the GV 20 group, and the no applied EA group and LI 4 group showed similar level. Conclusions: EA stimulation in the initial step after ischemia seems to affect positively Bax and Caspase-3 expression that are index of forebrain apoptosis.

• 농업생명과학연구
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• 제46권6호
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• pp.137-146
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• 2012

본 연구는 중간대뇌동맥을 폐쇄한 대뇌허혈성 손상모델에서 ferulic acid에 의해 조절되는 HO-1과 HO-2의 발현에 관하여 조사하였다. 흰쥐(Sprague-Dawley, 수컷)에 ferulic acid (100 mg/kg) 또는 vehicle을 중간대뇌동맥폐쇄술(MCAO) 후 정맥으로 주사하였고 중간대뇌동맥폐쇄술(MCAO)을 실시한 24시간 후 대뇌피질의 조직을 적출하였다. Hematoxylin과 eosin 염색을 통하여 MCAO로 유도된 뇌 손상시 ferulic acid의 보호효과를 확인하였다. MCAO을 시행한 대뇌피질에서는 응축된 핵과 신경세포의 괴사 소견을 보였으나, ferulic acid 투여군에서는 이들 신경세포의 병변을 현저히 완화시켰다. HO-1과 HO-2의 RNA와 단백질 발현의 변화를 reverse-transcription PCR과 Western blot으로 분석하였다. HO-1 발현은 MCAO 후 vehicle 투여군에서 현저히 감소하였으나, MCAO 후 ferulic acid를 투여한 실험군에서는 이들 감소의 완화를 보였으며, MCAO를 시행하지 않은 실험군의 수준으로 유지되었다. 그러나, HO-2의 발현은 MCAO 후 vehicle 투여군과 ferulic acid 투여군에서 유의적인 차이는 관찰되지 않았고 MCAO를 시행하지 않은 실험군의 수준으로 유지되었다. 따라서, 본 연구의 결과는 허혈성 뇌 손상시 ferulic acid는 HO-1 발현을 조절하였으나, HO-2의 발현에는 영향을 미치지 못함을 확인하였다. 결론적으로, 허혈성 뇌손상시 ferulic acid는 HO-1의 발현을 조절하여 신경세포를 보호하는 역할을 수행한다는 사실을 확인하였다.

• Korean Journal of Radiology
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• 제19권6호
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• pp.1161-1171
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• 2018

Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true "at risk" penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset. Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain. Results: The mean volume of oligemia was $24.7{\pm}14.1mm^3$, that of TP was $81.3{\pm}62.6mm^3$, and that of IC was $123.0{\pm}85.2mm^3$ at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences (p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points. Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

• Clinical and Experimental Pediatrics
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• 제52권7호
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• pp.824-831
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• 2009

목 적 : HIE의 치료법으로 줄기 세포가 대안으로 떠오르고 있다. mMSC가 성인 동물 모델에서의 뇌졸중 및 퇴행성 뇌질환에 유의한 기능 회복을 보인다는 보고가 많이 있으나 미성숙 동물 모델에서의 연구 보고는 거의 없는 상태이다. 이에 HIE가 유발된 미성숙뇌에 mMSC를 투여하여 기능 회복에 대한 효과를 평가하고자 본 연구를 시행하였다. 방 법 : 생후 7일된 수컷 Sprague-Dawley 흰쥐를 sham 대조군, 뇌 손상 대조군, 고용량 mMSC 이식군 및 저용량 mMSC 이식군으로 나누었으며 저산소 허혈 뇌 손상 유도 2주 후에 mMSC를 병변부 국소 이식을 시행하였다. 세포 이식 2, 4, 6 및 8주째에 개방장 시험을 시행하여 운동 기능 회복 정도를 평가하였고, 이후 1주일 동안 Morris 수중 미로 시험을 3개 부문으로 시행하여 학습 및 기억력 회복 정도를 평가하였다. 결 과 : 개방장 시험 결과 네 군간에서 통계적으로 유의한 차이는 없었다(F=0.412, P=0.745). 공간 획득 검사에서 네 군간 평균 탈출 시간에 서로 차이가 있었고(F=380.319, P<0.01), 고용량 mMSC 이식군 및 sham 대조군은 뇌 손상 대조군에 비해 검사 2일째부터 5일째까지 각각 평균 탈출 시간이 감소하였으며(P<0.05), 시간이 갈수록 더 유의하게 차이를 보였다(F=16.034, P<0.01). 참조 기억 검사에서는 네 군간 차이는 없었으며 시각 검사에서는 다섯번째 시행 검사에서만 고용량 mMSC 이식군과 뇌 손상 대조군간에 통계적으로 유의한 차이가 있었다(P<0.05). 결 론 : 일부 검사에서만 고용량 mMSC 이식의 효과가 뚜렷하였고 그 외의 검사에는 통계적으로 유의한 결과는 보이지는 않았으나 산술적인 호전을 보이는 것을 확인할 수 있었다. 향후 최적의 효과를 보이는 줄기 세포의 농도와 이식 시기를 결정하는 연구가 필요할 것으로 보이며 HIE에서 mMSC가 대안적인 치료 수단으로 이용될 수 있다고 생각된다.