• 대한임상검사과학회지
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• 제43권4호
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• pp.179-187
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• 2011

Animal models are important tools in thrombosis research and preclinical drug development. In recent studies, ferric chloride ($FeCl_3$) has been widely used to induce arterial thrombosis in a variety of species. The purpose of this study was to find an optimal concentration of $FeCl_3$ and validate this model suited better for thrombosis research. A small piece of filter paper, soaked in $FeCl_3$ solution (10, 20 or 35%, v/v, in distilled water) was topically applied on the carotid artery of SD rats to measure the time to occlusion (TTO) and thrombus weight (TW) to ascertain 35%, as an optimal $FeCl_3$ concentration ($8.63{\pm}0.92min$; p =0.000, $0.79{\pm}0.03mg/mm$; p =0.000, respectively). To validate this experimental model, Ginkgo biloba special extract EGb761 (5, 10 or 30 mg/kg) as a reference agent administered by peritoneal route for 1h prior to the induction of thrombosis, showed significantly delayed TTO in a dose dependent manner ($18.50{\pm}2.17$, $29.17{\pm}1.83$, and $38.00{\pm}1.79min$, respectively) and significantly reduced TW and repaired collagen fibre in the injured vessel compare to vehicle group. Our results provide a simple, reproducible and well controlled in vivo screening system to induce thrombosis in rats by the topical application of 35% $FeCl_3$ to assess the efficacy of the new anti-thrombotic agents.

• Journal of Chest Surgery
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• 제45권2호
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• pp.73-79
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• 2012

Background: Aortic cross clamping is associated with spinal cord ischemia. This study used a rat spinal cord ischemia model to investigate the effect of distal aortic pressure on spinal cord perfusion. Materials and Methods: Male Sprague-Dawley rats (n=12) were divided into three groups. In group A (n=4), the aorta was not occluded. In groups B (n=4) and C (n=4), the aorta was occluded. In group B the distal aortic pressures dropped to around 20 mmHg. In group C, the distal aortic pressure was decreased to near zero. The carotid artery and tail artery were cannulated to monitor the proximal aortic pressure and the distal aortic pressure. Fluorescent microspheres were used to measure the regional blood flow in the spinal cord. Results: After aortic occlusion, blood flow to the cervical spinal cord showed no significant difference among the three groups. In groups B and C, the thoracic and lumbar spinal cord and renal blood flow decreased. No microspheres were detected in the thoracic and lumbar spinal cord of group C. Conclusion: The spinal cord blood flow is dependent on the distal aortic pressure after thoracic aortic occlusion.

• Preventive Nutrition and Food Science
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• 제19권3호
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• pp.145-155
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• 2014

Vascular dementia is characterized by white matter lesions involving the demyelination and activation of astrocytes and microglia. In a previous study, we showed that the supernatant of a laboratory-scale, hot water extract of ground whole wheat (TALE) attenuated white matter injury and astrocytic activation in a rat model of bilateral common carotid artery occlusion (BCCAO). In the present study, we made several modifications to the hot water extraction process to remove starch and enable large-scale production. We used wheat bran (WB), which contains less starch, instead of ground whole wheat. In addition, we removed starch granules with a decanter before hot water extraction. The final product, wheat bran extract (WBE), contained 2.42% arabinose, a surrogate marker of arabinoxylan, which is an active constituent of WBE. Supplementation of the rat model of BCCAO with WBE (400 mg/kg/day) for 33 days attenuated white matter injury, which was assessed by Luxol Fast Blue staining, in the corpus callosum (cc) and optic tract (opt) regions. Attenuation of white matter injury in the opt region was accompanied by improvement of the pupillary light reflex. Immunochemical staining revealed that supplementation with WBE reduced astrocytic activation in the cc and opt regions and reduced microglial activation in the opt region. These findings indicate that supplementation with WBE is effective at attenuating white matter injury accompanied by the inhibition of astrocytic and microglial activation. Therefore, extracts from WB, a cheap by-product of wheat milling, can be developed as a nutraceutical to prevent vascular dementia, a disease for which there is no approved pharmaceutical treatment.

• 대한본초학회지
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• 제28권5호
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• pp.33-38
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• 2013

Objectives : The aim of this study was to examine anti-thrombotic effect of traditional herbal extracts in a rat model of ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis. Methods : Thirty minutes prior to a 35% $FeCl_3$ application, Sprague Dawley(SD) rats were injected with the 10 types of traditional herbal extracts (100mg/kg, intraperitoneal injection), respectively. The effect of these herbal extracts was examined for time to occlusion(TTO) using the Laser doppler flow meter and measured for thrombus weight (TW) in $FeCl_3$-induced thrombosis model. Results : In the TTO, Salvia miltiorrhiza (Sm, $2.30{\pm}0.28$ min, p<0.001) and Santalum album (Sa, $2.19{\pm}0.19$ min, p<0.001) showed significantly delayed TTO more than twice compared with Saline-treated group. Cnidium officinale (Co), Psoralea corylifolia (Pc), Scutellatia baicalensis (Sba), Panax notoginseng (Pn), Angelica tenuissima (At), Scrophularia buergeriana (Sbu), Rhus verniciflua (Rv) and Picrasma quassioides (Pq), except for Rhus verniciflua (Rv) also meaningfully impeded TTO more than one fold. In addition, Salvia miltiorrhiza, Santalum album, Cnidium officinale, Psoralea corylifolia and Scutellatia baicalensis significantly reduced TW more than 10% compared with Saline-treated group. Especially, Salvia miltiorrhiza and Santalum album showed the most excellent anti-thrombotic effect among the 10 herbal extracts tested on the restoration of altered TTO and TW. Conclusions : These results suggest that Sm and Sa extracts have outstanding anti-thrombotic effect in $FeCl_3$-induced thrombosis model and is potentially useful as herbal medicines for the treatment and prevention of thrombosis.

• 대한간호학회지
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• 제49권3호
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• pp.317-328
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• 2019

Purpose: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. Methods: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered $80{\mu}g/kg$ ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. Results: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. Conclusion: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.

• 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.

• 국제물리치료학회지
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• 제1권2호
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• pp.107-112
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• 2010

The majority of strokes are caused by ischemia and result in brain tissue damage, leading to problems of the central nervous system including hemiparesis, dysfunction of language and consciousness, and dysfunction of perception. The purpose of this study was to investigate the effects of Poly(ADP-ribose) polymerase(PARP) on necrosis in neuronal cells that have undergone needle electrode electrical stimulation(NEES) prior to induction of ischemia. Ischemia was induced in male SD rats(body weight 300g) by occlusion of the common carotid artery for 5 min, after which the blood was reperfused. After induction of brain ischemia, NEES was applied to Zusanli(ST 36), at 12, 24 and 48 hours. Protein expression was investigated using immuno-reactive cells, which react to PARP antibodies in cerebral nerve cells, and Western blotting. The results were as follows: In the cerebral cortex, the number of PARP reactive cells after 24 hours significantly decreased(p<.05) in the NEES group compared to the GI group. PARP expression after 24 hours significantly decreased(p<.05) in the NEES group compared to the GI group. As a result, NEES showed the greatest effect on necrosis-related PARP immuno-reactive cells 24 hours after ischemia, indicating necrosis inhibition, blocking of neural cell death, and protection of neural cells. Based on the results of this study, NEES can be an effective method of treating dysfunction and improving function of neuronal cells in brain damage caused by ischemia.

• 대한핵의학회지
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• 제30권4호
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• pp.484-492
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• 1996

허혈성 뇌 병변에서 $^{99m}Tc$-glucarate의 섭취에 관한 연구를 하기 위하여 중뇌동맥 폐쇄 쥐 뇌허혈 모델을 재관류한 군과 하지 않은 군으로 나누어 만들었다. $^{99m}Tc$-glucarate와 [$^{18}F$]FDG를 연속적으로 투여하여 그 분포 양상을 이중 자가방사촬영법으로 관찰하였다. 조직의 괴사 여부를 알기 위하여 TTC 염색도 실시하여 동일한 뇌표본에 대하여 3가지의 영상을 동시에 얻을 수가 있었다. 얻은 영상으로 섭취 또는 비섭취정도를 보아 0점에서 3점까지 점수를 매겨 합하여 비교하였다. 수술한 쥐들 18마리 중 10마리가 신경학적 증상을 보이면서 살아남아 실험대상이 되었다. TTC 염색으로 확인한 경색크기는 재관류하지 않은 군이 컸다. [$^{18}F$]FDG 섭취양상은 TTC 염색과 거의 비슷하였다. 다만 일부에서 TTC 염색되는 곳에 [$^{18}F$]FDG 가 중간정도로 섭취되는 곳이 있었고 TTC 염색되지 않는 곳에 [$^{18}F$]FDG가 중간정도 섭취되는 곳이 있었다. TTC로 염색된 부위에는 $^{99m}Tc$-glucarate가 섭취되지 않았다. TTC로 염색되지 않는 곳에 일부분 $^{99m}Tc$-glucarate가 섭취되었다. TTC와 [$^{18}F$]FDG가 염색되거나 섭취되지 않는 곳에 $^{99m}Tc$-glucarate가 섭취되지 않는 곳이 있었다. 그러나 [$^{18}F$]FDG의 중간 정도의 섭취나 [$^{18}F$]FDG와 TTC사이에 부합하지 않는 곳 등과 $^{99m}Tc$-glucarate 섭취와 대응시키기 어려웠다 $^{99m}Tc$-glucarate가 재관류 군에서 더 넓고 많이 섭취되었다. 결론적으로 $^{99m}Tc$-glucarate는 비생존 허혈조직에만 섭취되는데 관류재개통에 따라 다양하게 섭취되었고 재관류모델에 더 많이 넓게 섭취되었다. 중뇌동맥폐색 및 재관류 모델로 $^{99m}Tc,\;^{18}F$ 및 TTC 동시영상을 얻어 생존능과 포도당대사의 부합 비부합 여부를 밝히고 그 의의를 조사한 후 $^{99m}Tc$-glucarate섭취와 상관을 조사하면 $^{99m}Tc$-glucarate섭취의 의의를 밝힐 수 있을 것으로 본다.

• Archives of Pharmacal Research
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• 제26권3호
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• pp.224-231
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• 2003

The anti-thrombotic effects of LB30057, a direct thrombin inhibitor, were evaluated with in vivo rat and dog thrombosis models. In rats, 1 mg/kg of LB30057 inhibited half of the clot formations in the inferior vena cava at 5 minutes after intravenous application. When measured at 2 hours after oral application, 100 mg/kg prevented approximately half of the clot formations in the inferior vena cava and 50 mg/kg prolonged the mean occlusion time from $15.6{\pm}1.3$ minutes to $47.2{\pm}8.3$ minutes in the carotid artery. In dogs, the formation of thrombus in the jugular vein was reduced to half at a dose range of 20-30 mg/kg at 6 hours after oral application. In addition, the LB30057 dosage required to reduce venous clot formation by approximately 80-90% in dogs was only about 10% of that required for the same reduction in rats. This is probably due to the variation in its time-dependent blood concentration profiles in each species; for example, the plasma half-life of LB71350 in dogs was longer than that in rats ($153.0{\pm}3.0$ vs. $129.7{\pm}12.7$ min at 30 mg/kg, i.v., respectively). AUG, $T_{max},{\;}G_{max}$, and BA in dogs were 59, 8.9, 9.17, and 13.3 times higher than those in rats at oral 30 mg/kg, respectively. Taken together, these results suggest that LB30057 administered orally is effective in the prevention of arterial and venous thrombosis in rats and dogs. It therefore represents a good lead compound for investigations to discover a new, orally available, therapeutic agent for treating thrombotic diseases.

• 동의생리병리학회지
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• 제36권2호
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• pp.59-65
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• 2022

Rodent model for chronic cerebral hypoperfusion caused by bilateral carotid artery occlusion (BCAO) show clinically relevant evidences for vascular dementia and impairments of synaptic plasticity in the hippocampus. The purpose of this study was to evaluate effect of fermented garlic (F-Garlic) extract with NO metabolites on cognitive behaviors, synaptic plasticity, and molecular events in the hippocampus following BCAO. Adult male Sprague-Dawley rats were randomly divided three experimental groups into: control+water; BCAO+water; BCAO+F-Garlic. Animals were treated with oral administration of F-Garlic in tap water as a drinking water after surgery for 4 weeks. On passive avoidance test and Y-maze test, BCAO+water showed a significant decrease in step-through latency and spontaneous alteration, indicating deficit of hippocampal memory formation but the treatment of F-Garlic significantly increased these cognitive behaviors. In control+water, a robust increase in the amplitude of evoked field excitatory postsynaptic potentials was observed by theta burst stimulation to hippocampal neural circuit indicating formation of long-term potentiation (LTP) in the hippocampal CA1. BCAO+water showed a highly significant deficit in LTP induction 4 weeks after BCAO. On other hand, daily oral administration of F-Garlic extract caused the marked preservation of LTP induction. Moreover, parvalbumin was markedly reduced in the CA1, especially, in the stratum radiatum of BCAO+water. In contrast, BCAO+F-Garlic mitigate a significantly reduction of the parvalbumin. In summary, these results suggest that daily oral administration of F-Garlic extract can ameliorate cognitive memory deficit through the preservation of synaptic plasticity and interneurons integrity in the hippocampus in rodent model of chronic cerebral hypoperfusion.