• 사상체질의학회지
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• 제13권2호
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• pp.165-176
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• 2001

This study demonstrates the effects of Yanggyuksanhwa-Tang, Sasang constitutional herb prescription reported its clinical effect on the stroke of the So-yang In(少陽人), on the cerebral blood flow changes induced by nitro L-arginine methyl ester (L-NAME) treatment and ischemic brain damage induced by the middle cerebral artery occlusion (MCAO) in the rats. The changes of the arterial blood pressure, cerebral blood flow, and the diameter of the pial artery were measured in rats treated with L-NAME. And the changes of the infarct size, volume, and plasma tumor necrosis factor alpha ($TNF-{\alpha}$) levels were measured in the rats that the middle cerebral artery has been occluded by the intraluminal suture thread method. Yanggyuksanhwa-Tang was administered by the i.v. injection on the L-NAME treated rats, by the i.o. administration on the MCAO rats. The results is 1. The changes of the arterial blood pressure was not different statistically between in the L-NAME treated control group and in the Yanggyuksanhwa-Tang administered group. 2. Increase in the cerebral blood flow induced by L-NAME treatment was attenuated in the Yanggyuksanhwa-Tang administered group significantly (P<0.05) as compared with the L-NAME treated control group. 3. Decrease in the diameter of the pial artery induced by L-NAME treatment was attenuated about 18% in the Yanggyuksanhwa-Tang administered group as compared with the L-NAME treated control group. 4. Ischemic damaged infarct areas were decreased significantly (P<0.05) in the interaural 12mm, 10mm, and 6mm brain sections of the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group. 5. Total ischemic infarct volume was decreased significantly (P<0.05) in the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group. 6. Plasma $TNF-{\alpha}$ levels were decreased significantly (P<0.01) in the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group.

• Advances in Traditional Medicine
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• 제8권4호
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• pp.430-439
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• 2008

Chungpaesagan-tang (CPSGT) is most frequently used to treat ischemic brain injury in tradition Korean medicine. Clinically, cerebral ischemia is likely to be accompanied by preexisting or complicating disease. However, animal models used to examine the effects of herbal medicines on cerebral ischemia have not given this issue sufficient consideration. The present study was undertaken to determine the effects of CPSGT on focal cerebral ischemia in normal and SHR rats subjected to transient middle cerebral artery occlusion (MCAO). Animals were divided into four groups: Normal (Sprague-Dawley) rats subjected to MACO (the NC+MCAO group), normal rats subjected to MCAO and then administered CPSGT (NC + MCAO + CP), SHR rats subjected to MCAO (SHR + MCAO), and SHR rats subjected to MCAO and then administered CPSGT (SHR + MCAO + CP). MCAO was performed using the intraluminal method. CPSGT was administrated orally twice (1 and 4 h) after MCAO. All animals were sacrificed at 24 h postoperatively. Brain tissues were stained with hematoxylin & eosin, to examine the effect of CPSGT on ischemic brain tissues. In addition, changes in TNF-$\alpha$ expression in ischemic areas were examined by immunostaining. CPSGT was found to significantly reduce infarction areas in normal and SHR rats and infarction volumes in SHR rats. Similarly, CPGST markedly increased neuron numbers and sizes in all treated groups, except cell sizes in SHRs. Furthermore, CPSGT reduced TNF-$\alpha$ expression in MCAO administered SHR rats. The findings of the present study suggest that CPSGT effectively ameliorates neuron damage caused by MACO-induced cerebral ischemia, and that it has a significant neuroprotective effect after cerebral ischemia in SHR.

• 대한본초학회지
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• 제29권3호
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• pp.71-78
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• 2014

Objectives : This study evaluates the neuroprotective effects of Sopung-tang, a mixture of Notopterygii Rhizoma, Saposhnikoviae Radix, Angelicae Gigantis Radix, Cnidii Rhizoma, Hoelen, Aurantii Nobilis Pericarpium, Pinelliae Tuber, Linderae Radix, Angelicae Dahuricae Radix, Cyperi Rhizoma, Cinnamomi Ramulus, Asari Radix, Glycyrrhizae Radix on the cerebral infarct combined with hyperlipidemia. Method : The hyperlipidemia was induced by the beef tallow 30% diet for 14 days on Sprague-Dawley rats. The cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with intraluminal thread method. Then the water extract of Sopung-tang was administered a day for 5 days at 3 hours after the cerebral infarct by MCAO. Effect of Sopung-tang was evaluated with the infarct volume and edema percentage by a TTC-stained brain section, and the expressions of Bax and Bcl-2 in the brain tissue by a immunohistochemical stain method. Results : Sopung-tang reduced the infarct size partly in a TTC-stained brain section of the hyperlipidemic MCAO rats. Sopung-tang reduced the infarct volume of the hyperlipidemic MCAO rats significantly. Sopung-tang reduced the edema percentage of the hyperlipidemic MCAO rats, but not significant statistically. Sopung-tang suppressed the Bax expressions in the cerebral penumbra and caudate putamen of the hyperlipidemic MCAO rats significantly. Sopung-tang upregulated the Bcl-2 expression in the caudate putamen of the hyperlipidemic MCAO rats. Conclusion : These results suggest that Sopung-tang plays an anti-apoptotic neuroprotective effect through the suppression of Bax and up-regulation of Bacl-2 expressions in the brain tissues.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.272-278
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• 2017

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-${\alpha}$), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.

• 대한본초학회지
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• 제29권5호
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• pp.23-30
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• 2014

Objectives : Dodam-tang has been reported to have a control effect against the hyperlipidemia and thrombosis. Based upon these previous reports, this study investigates the effects of Dodam-tang on the cerebral ischemic damage of the hyperlipidemic rats. Methods : Hyperlipidemia was induced by the beef tallow 30% diet for 14 days on Sprague-Dawley rats. Ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with the intraluminal thread method. Then water extract of Dodam-tang was administered daily for 5 days. The effect of Dodam-tang was evaluated with the serum lipids, infarct volume and edema percentage, and immunohistochemical expressions of iNOS, MMP-9, and GFAP in the brain tissue. Results : The obtained results were as follows; Dodam-tang reduced significantly the infarct size in a TTC-stained 5th brain section of the hyperlipidemic MCAO rats. Dodam-tang suppressed the infarct volume of the hyperlipidemic MCAO rats, but not significant statistically. Dodam-tang suppressed the edema percentage of the hyperlipidemic MCAO rats significantly in the brain tissue. Dodam-tang suppressed significantly the iNOS expression in the cerebral penumbra and caudate putamen of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the MMP-9 expression in the cerebral penumbra of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the GFAP-expressed atrocytes in the cerebral penumbra of the hyperlipidemic MCAO rats. Conclusions : These results suggest that Dodam-tang suppresses the brain edema formation through the suppression of the iNOS, MMP-9 and GFAP, but the neuroprotective effect against the cerebral infarct are not distinct.

• Journal of Korean Neurosurgical Society
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• 제40권3호
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• pp.180-185
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• 2006

Objective : Middle cerebral artery occlusion[MCAO] has widely been used to produce ischemic brain lesions. The lesions induced by MCAO tend to be variable in size because of the variance in the collateral blood supply found in the mouse brain. To establish a less invasive and reproducible focal ischemia model in mice, we modified the technique used for rat photo thrombosis model. Methods : Male C57BL/6 mice were subjected to focal cerebral ischemia by photothrombosis of cortical microvessels. Cerebral infarction was produced by intraperitoneal injection of Rose Bengal, a photosensitive dye and by focal illumination through the skull. Motor impairment was assessed by the accelerating rotarod and staircase tests. The brain was perfusion-fixed for histological determination of infarct volume four weeks after stroke. Results : The lesion was located in the frontal and parietal cortex and the underlying white matter was partly affected. A relatively constant infarct volume was achieved one month after photothrombosis. The presence of the photothrombotic lesion was associated with severe impairment of the motor performance measured by the rotarod and staircase tests. Conclusion : Photothrombotic infarction in mice is highly reproducible in size and location. This procedure can provide a simple method to produce cerebral infarction in a unilateral motor cortex lesion. In addition, it can provide a suitable model for study of potential neuroprotective and therapeutic agents in human stroke.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.149-157
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• 2017

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

• 대한간호학회지
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• 제36권7호
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• pp.1232-1241
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• 2006

Purpose: The purpose of this study was to examine the effects of cerebral ischemia on Type I(soleus) and Type II(plantaris, gastrocnemius) muscles, and to determine the effects of isometric contraction training by electro- stimulation on Type I and II muscles in cerebral ischemia model rats. Method: Twenty-five male Sprague-Dawley rats were randomly divided into four groups: ST(stroke), STES(stroke+electrostimulation), SH(sham) and SHES (sham+electrostimulation). The ST and STES groups received a transient right middle cerebral artery occlusion operation. The SH and SHES groups received a sham operation. The STES and SHES groups had daily isometric contraction training by electrostimulation(100Hz, 45mA, 7.5V) on hindlimb muscles for 7days. Result: Plantaris and gastrocenmius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the muscle fiber cross-sectional area of gastrocnemius in the ST group significantly decreased compared with the SH group. Soleus, plantaris, gastrocnemius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the Type I muscle fiber cross-sectional area of soleus and the Type II muscle fiber cross-sectional area of gastrocnemius in the STES group significantly increased compared with the 57 group. Conclusion: Hindlimb muscle atrophy occurs after acute stroke and isometric contraction training by electrostimulation during early stages of a stroke attenuates muscle atrophy of Type I and Type II muscles.

• 혜화의학회지
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• 제9권1호
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• pp.387-397
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• 2000

연구배경(硏究背景): He-Ne laser 정맥혈관내(靜脈血管內) 조사(照射) (Intravascular Laser Irradiation of Blood : ILIB)가 말초(末梢) 및 뇌혈관순환장애(腦血管循環障碍), 뇌기능장애(腦機能障碍), 동맥경화(動脈硬化) 등의 예방(豫防)과 치료(治療) 목적(目的)으로 사용(使用)되고 있으나 이에 대한 한의학(韓醫學)에서의 연구(硏究)는 찾아보기 힘들다. 이에 저자(著者)는 발병(發病) 48시간(時間) 이내(以內)에 내원(來院)하여 뇌전산화단층촬영(腦電算化斷層撮影)으로 진단(診斷)된 초기(初期) 뇌경색(腦梗塞) 환자(患者)에서 ILIB의 효과(效果)를 평가(評價)하고자 본(本) 연구(硏究)를 시행(施行)하였다. 아울러 흰쥐의 국소(局所) 뇌허혈(腦虛血)에 미치는 영향(影響)을 측정(測定)하였다. 방법(方法) : 대상(對象) 환자(患者) 40명(名)을 UC-SHJGS(우황청심환(牛黃淸心丸)-성향정기산(星香正氣散))만을 투여(投與)한 대조군(對照群)과 UC-SHJGS 투여(投與)와 ILIB를 병용(倂用)한 치료군(治療群)으로 나누어 시행(施行)하였다. 대상환자(對象患者)는 모두 변증(辨證)과 무관(無關)하게 UC, SHJGS만을 투여(投與)하고 침치료(鍼治療)는 중풍칠처혈(中風七處穴)로 한정(限定)하였으며 5일간(日間)의 치료기간(治療期間) 동안 치료군(治療群)에서는 출력(出力) 1.8-2.5mW의 He-Ne laser를 1일(日) 1회(回) 50분(分) 동안 조사(照射)하였다. 동물실험(動物實驗)은 흰쥐를 대상(對象)으로 중대뇌동맥(中大腦動脈)을 결찰(結紮)하여 국소(局所) 뇌허혈(腦虛血)을 유발(誘發)하고 대조군(對照群)과 ILIB를 실시(實施)한 실험군(實驗群)으로 나누어 그 허혈면적(虛血面積)과 부종율(浮腫率)을 측정(測定)하였다. 결과(結果) : 1. 증상호전지수(症狀好轉指數)는 대조군(對照群)과 치료군(治療群) 사이에 유의(有意)한 차이(差異)가 없었다. 2. 치료전후(治療前後) 측정(測定)한 내경동맥(內頸動脈) siphon부(部)의 혈관반응성(血管反應性)은 대조군(對照群)과 치료군(治療群)에서 모두 유의성(有意性)있는 변화(變化)가 없었다. 3. 치료전후(治療前後) 측정(測定)한 요골동맥(橈骨動脈)의 혈관반응성(血管反應性)은 대조군(對照群)과 치료군(治療群)에서 모두 유의성(有意性) 있는 변화(變化)가 없었다. 4. 치료전후(治療前後) 측정(測定)한 PT, a-PTT은 대조군(對照群)과 치료군(治療群)에서 모두 유의성(有意性)있는 변화(變化)가 없었고, fibrinogen은 치료군(治療群)에서 치료전(治療前)보다 유의성(有意性) 있게 증가(增加)하였으나 평균값이 정상(正常) 범위(範圍)에서 벗어나지 않았다. 5. 국소(局所) 뇌허혈(腦虛血) 동물(動物) 실험(實驗)에서는 실험군(實驗群)에서 신경학적(神經學的) 결손(缺損), 허혈(虛血) 면적율(面積率), 부종율(浮腫率)이 유의성(有意性)있게 감소(減少)하였다 결론(結論) : 이상(以上)의 연구(硏究) 결과(結果) 뇌경한(腦硬寒)의 초기(初期) 치료(治療)에서 기존(旣存)의 한의학(韓醫學) 치료(治療)에 ILIB를 추가(追加)하는 것이 치료(治療) 효과(效果)를 증가(增加)시킨다는 증거(證據)는 없었으며 동물(動物) 실험(實驗)에서는 뇌경색(腦梗塞)의 치료(治療)에 응용(應用)할 수 있는 가능성(可能性)을 보여주고 있으나 그 효과(效果)와 적응증(適應症)을 구체적(具體的)으로 증명(證明)하기 위한 체계적(體系的)이고 다양(多樣)한 임상실험(臨床實驗)이 지적(持績)되어야할 것으로 생각된다.

• 대한한의학회지
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• 제21권2호
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• pp.25-36
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• 2000

Objectives : This study demonstrates the effects of Daejo-hwan on learning and memory impairment induced by L-NAME (75 mg/kg) treatment and on cerebral ischemic damage induced by middle cerebral artery (MCA) occlusion in rats. Methods : Daejo-hwan emulsion (73.3 mg/100 g/l ml) was administered to rats along a timed study schedule. The Moms water maze was used for learning and memory test of the rats. The MCA was occluded by using the intraluminal thread method. The brain slices were stained by 2 % triphenyl tetrazolium chloride (TTC) and 1 % cresyl violet solution. Infarct size, neuron cell number and size in penumbra was measured by using computer image analysis system. Results : 1. The escape latency of the Daejo-hwan treated group decreased significantly with respect to the control group. 2.The memory score of the Daejo-hwan treated group showed increase tendency, And the swimming distance was not different between the normal, the control, and the Daejo-hwan treated group. 3. The infarct size of the Daejo-hwan treated group decreased significantly with respect to the control group. 4. The total infarct volume of the Daejo-hwan treated group showed decrease tendency. And the brain edema index of the Daejo-hwan treated group decreased significantly with respect to the control group. 5. The neuron cell number and cell size in penumbra of the Daejo-hwan treated group increased significantly with respect to the control group. Conclusions : According to the above results, it is supposed that Daejo-hwan is clinically applicable to the vascular dementia.