• Journal of Korean Neurosurgical Society
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• 제37권1호
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• pp.54-58
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• 2005

Objective: The purpose of this study is to determine the time evolution and distribution of cerebral apoptosis using the middle cerebral artery occlusion model in rats. Methods: A total of twenty four male rats - with 2, 3, 4, 6, 8, 12, 24 and 48 hours of middle cerebral artery occlusion respectively - were studied. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling(TUNEL) method was used for the observation of the apoptotic cells. The apoptotic ratio was calculated and the distribution of apoptosis was inspected in the pyriform cortex, basal ganglia and middle cerebral artery territory cortex. The rats were divided into three groups(Group I : $2{\sim}4$ hours of occlusion, Group II : $6{\sim}$12 hours of occlusion, Group III : $24{\sim}48$ hours of occlusion). Results: In this study, the proportion of apoptosis increased with the duration of middle cerebral artery occlusion and reached a maximum after about 12 hours of middle cerebral artery occlusion. The mean values of the apoptotic ratio were $30.7{\pm}11.3%$ in group I, $60.8{\pm}2.6%$ in group II and $48.7{\pm}0.7%$ in group III. The distribution of apoptosis differed in the pyriform cortex, basal ganglia and middle cerebral artery territory cortex according to the duration of time of the middle cerebral artery occlusion. Conclusion: In the middle cerebral artery occlusion model of the rats, apoptosis is found to increase according to the occlusion time, reaching a peak after 6 hours, and the distribution of apoptosis changed from the pyriform cortex to the basal ganglia and middle cerebral artery territory cortex.

• 한국콘텐츠학회논문지
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• 제19권7호
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• pp.186-191
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• 2019

서론: 최근 노년층에서 뇌졸중 발병률이 증가하고 있다. 현재 뇌졸중 치료제 및 방법이 많이 개발되어 있으나 치료 후에도 후유증 등이 많이 남게 된다. 그래서 아직도 많은 과학자나 임상 의사들이 이를 치료하기 위한 약물 및 방법을 연구하고 있는 실정이다. 많은 연구 중 뇌졸중 치료 연구를 위한 표준화된 실험 동물연구는 드물며, 표준화된 Nylon thread를 이용한 중대뇌동맥 폐쇄모델(MCAO, middle cerebral artery occlusion)의 성공률에 대한 연구는 거의 없다 방법: 본연구는 $0.18{\pm}0.02mm$의 지름을 가진 5-0 Nylon thread를 중대뇌동맥에 삽입하였다. 60분 동안 삽입한 후에 봉합해 놓았던 부위를 다시 절개하여 Nylon thread를 빼내고, 막았던 혈관의 매듭을 풀어주어, 다시 혈액이 공급되게 하였다. 그로부터 23시간 후에 뇌를 내어 1mm 두께로 자른 후 1.5% TTC(2',3',5'-triphenyl-tetrazolium chloride)로 15분간 염색하고, 4% PFA(paraformaldehyde)로 15분 동안 고정하였다. 결과: Nylon thread를 삽입하여, MCA occlusion 50마리, ICA occlusion 14마리, 제대로 된 MCAO model보다 좀 더 깊게 들어간 distal MCAO model 36마리, 너무 깊은 MCA나 ACA까지 들어가서 상보적인 괴사를 나타내는 occlusion model 1마리, 그리고 경색이 일어나지 않은 마우스 50마리를 확인하였다. 결론: 이에 본 연구에서는 Nylon Thread를 생쥐의 무게에 따라 32~36g 인 생쥐는 9mm로 삽입하여주고, 37~40g인 생쥐는 9mm+0.5mm의 깊이로 삽입하여서 1hr의 occlusion과 23hr의 reperfusion을 주어 생쥐를 TTC 염색을 통하여 괴사가 일어난 부분을 확인하였고, 생쥐에서 가역적인 뇌혈관 경색으로 151말중 101마리에서 뇌경색을 유도 할 수 있었다(66.9%).

• 대한한의학회지
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• 제20권4호
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• pp.82-92
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• 2000

The purpose of the present study was to explore the proper method for animal stroke model of Oriental medicine To this end, brain ischemia was induced by distal middle cerebral artery occlusion(dMCAO) and proximal middle cerebral artery occlusion(pMCAO) and evaluated with the method of Triphenyl Tetrazolium Chloride (TTC) staining and Swimming Behavior Test. Results demonstrated that first, infarct size and volume of pMCAO group were significantly bigger that those of dMCAO group. Second, analysis of swimming behavior test revealed that the percentage of left turning angles of pMCAO was significantly bigger than that of dMCAO. Third, during swimming behavior test, there were peculiar traces of small successive circles that represent motor dysfunction and conscious disturbance among dMCAO group. The results of the study thus indicate that non-invasive intraluminal method of pMCAO was the appropriate animal stroke model for Oriental medicine in the light of brain ischemia as hemiplesia and conscious disturbance.

• 대한한의학회지
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• 제21권2호
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• pp.68-78
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• 2000

Objective : This research was performed to investigate protective effects of Sophora subprostrata, against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was estimated using histological test, neurobehavioural test, and biochemical test. Methods : Rats(Sprague-Dawley) were divided into four groups: Sham operated group, MCA occluded group, Sophora subprostrata administrated group after MCA occlusion, and Normal group. The MCA was occluded by intraluminal method. Sophora subprostrata was administrated orally twice(l and 4 hours) after middle cerebral artery occlusion. The neurobeavioural test was performed at 3 hours, 6 hours, 9 hours and 24 hours after the surgery by posture reflex test and swimming behavioural test. All groups were sacrificed at 24 hours after the surgery. The brain tissue was stained with 2% triphenyl tetrazolium chioride(TTC) or 1 % cresyl violet solution, to examine effect of Sophora subprostrata on ischemic brain tissue. The blood samples were obtained from the heart of rats. Tumor necrosis factor-a level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). Results : The results showed that (1) Sophora subprostrata reduced infarct size and total infarct volume by 54.8% compared to the control group, (2) that neuronal death, which was shown by decrease in cell number and size, was attenuated significantly in the boundary area of the infarction, (3) that serum $TNF-{\alpha}$ㆍlevel was reduced significantly, and finally, there was significant recovery of motor deficit at 3 hours after MCA occluded by Swimming behavioural test. Conclusions :In conclusion, Sophora subprostrata has protective effects against ischemic brain damage at the early stage of ischemia.

• 대한한의학회지
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• 제22권1호
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• pp.10-21
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• 2001

Objective : This study was performed to investigate the protective effect of Stephania tetrandra(ST) against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was evaluated using histological tests, neurobehavioral tests, and biochemical tests. Methods : Rats(Sprague-Dawley) were divided into four groups : sham operated group, MCA occluded group, post MCA occlusion Stephania tetrandra administrated (7.6mg/l00g) group, and normal group. The MCA was occluded by intraluminal method. Stephania tetrandra was administrated orally twice at 1 and 4 hours after MCA occlusion. The neurobehavioral test was performed at 3, 6, 9 and 24 hours after MCA occlusion by posture reflex test and swimming behavioral test. All groups were sacrificed then. The brain tissues were stained with 2% triphenyl tetrazolium chloride(TTC) or 1 % cresyl violet solution, to examine infarct size, volume and cell number. Tumor necrosis $factor-{\alpha}$ level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). The mRNA expression level of inflammatory cytokines and related receptor type I and II, $IL-1{\beta}$, IL-6, and IL-10 6hours after MCA occlusion were also studied by reverse transcriptase polymerase chain reaction(RTPCR). Results : The results showed that : Stephania tetrandra (1) reduced infarct size and total infarct volume by 52.2% compared to the control group; (2) attenuated significantly in neuronal death, which was shown by a decrease in cell number(P<0.01) and size(P<0.01) in the boundary area of the infarction; (3) significantly reduced serum $TNF-{\alpha}$ level, and increased the mRNA level of IL-10 in the cortex region(P<0.01). However, there was no significant effect on motor deficit in swimming behavioral test. Conclusions : In conclusion, Stephania tetrandra has protective effects against ischemic brain damage at the early stage of ischemia.

• 한국임상수의학회지
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• 제33권1호
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• pp.10-15
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• 2016

The purpose of this study was to establish reproducible ischemic infarction model using allogenic blood clot in beagle dogs and identify induced ischemic lesion after middle cerebral artery occlusion using magnetic resonance imaging (MRI) and histopathologic findings. Twenty eight male beagle dogs with no evidence of neurologic disease were experimented. Allogenic embolus was made using a healthy beagle dog. After internal carotid artery (ICA) was exposure, 16G catheter was introduced through the ICA. The dog was administered 0.3 ml blood clot for 15 seconds followed by 3 ml of saline for 15 seconds. MRI scans were performed with 1.5T to evaluate ischemic lesion at 7 days after middle cerebral artery occlusion procedure. Evaluation parameters of MRI include location, distribution, infarction type, margin, shape, mass effect and intensity of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), fluid attenuated inversion recovery (FLAIR) sequence, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC). On MRI, all dogs (28/28) showed focal or multifocal lesion including telencephalon and thalamus lesions, especially caudate nucleus (24/28). These lesions had well-defined margin from adjacent brain parenchyma, none or mild mass effect and various shape. Most of dogs appeared hyperintensity on T1WI, T2WI, FLAIR, and DWI/ADC, corresponding to chronic infarction. These lesions were histopathologically confirmed atrophic changes and unstained lesion. In conclusion, MRI is the useful method to provide information about ischemic infarction in dogs and the best reproducible ischemic infarction model was developed by using allogenic blood clot.

• 한방재활의학과학회지
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• 제19권3호
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• pp.1-13
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• 2009

Objectives : This study evaluates neuroprotective effect of Gastrodiae Rhizoma on apoptosis in the cerebral infarct. Methods : Cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with intraluminal thread method in Sprague-Dawley rats. Then ethanol extract of Gastrodiae Rhizoma was administered orally for 3 days. Infarct area and volume were evaluated with TTC staining. Neuronal apoptosis was identified with TUNEL labeling. Apoptosis modulatory effect was observed with immunohistochemical Bax, Bcl-2, iNOS, and MMP-9 expressions in penumbra. Results : 1. Ethanol extract of Gastrodiae Rhizoma reduced infarct size partly and volume significantly of in the MCAO rat brain. 2. Ethanol extract of Gastrodiae Rhizoma reduced TUNEL positive cell ratio in the penumbra of MCAO rat brain significantly. 3. Ethanol extract of Gastrodiae Rhizoma suppressed Bax, iNOS and MMP-9 expression in the penumbra of MCAO rat brain significantly. 4. Ethanol extract of Gastrodiae Rhizoma did not change Bcl-2 expression in the penumbra of MCAO rat brain. But expression ratio of Bcl-2 against Bax was increased in the Gastrodiae Rhizoma group. Conclusions : These results suggest that Gastrodiae Rhizoma plays an anti-apoptotic neuroprotective effect through suppression of Bax, iNOS, and MMP-9 expressions and relative up-regulation of Bcl-2 in the ischemic brain tissue.

• 대한한의학회지
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• 제23권3호
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• pp.134-144
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• 2002

Objective : The purpose of this study was to investigate the effect of Jukryuk and Saengkang-juices on cerebral vascular ischemia (CVI) of the middle cerebral artery (MCA). Method : By admiuistration Jukryuk and Saengkang-juices, we compared treated groups with untreated groups, in view of five points as follows: 1) cerebral damage; 2) damaged area of ischemia; 3) cerebral edema; 4) the number of neuronal cells adjacent to the areas damaged by ischemia; and 5) the number of neuronal cells adjacent to the areas damaged by ischemia Results : In this experiment, the effect of Jukryuk and Saengkang-juices was determined by inducing cerebral vascular ischemia after occluding the middle cerebral artery (MCA) in mice, and making observations and comparisons such as alterations in damaged areas and neuronal cellular changes in the brain. Conclusions : According to the above results, Jukryuk and Saengkang-juices can protect the cerebral vascular ischemia.

• 대한핵의학회지
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• 제29권1호
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• pp.22-30
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• 1995

저자들은 두개 기저나 경부종괴 또는 내경동맥의 동맥류등으로 인하여 내경동맥의 결찰이 필요한 환자에 있어서 객관적인 관점에서 수술전에 영구적인 내경동맥의 결찰의 안전성에 관하여 $^{99m}Tc$-HMPAO 뇌 SPECT를 이용하여 보고자 하였다. 내경동맥의 결찰이 고려되는 24명의 두개기저나 경부종괴 환자를 대상으로 하였다. 저자들은 풍선 시험 결찰술 시행전과 시행중의 양측 중대뇌동맥 영역의 섭취정도를 $^{99m}Tc$-HMPAO 뇌 SPECT를 이용하여 비교해보았고 이러한 결과를 신경학적 검사, 경동맥 스텀프압 고리고 뇌전도검사등과 비교해 보았다. 대상환자중 19명의 환자에서는 풍선 시험 결찰술 동안 신경학적 이상등의 문제들을 경험하지 않았고 이들에 있어 중대뇌동맥영역의 섭취정도는 결찰술 시행전에 비교하여 95-101%에 해당하였다. 나머지 5명의 환자에서는 일과성 반신마비와 의식소실등의 심한 신경학적 증상을 보였고 이들에 있어 중대뇌동맥 영역의 섭취정도는 시행전에 비하여 77-85%에 해당하였으며 다른 검사결과와도 잘 부합되었다. 결론적으로 풍선시험결찰술 시행전과 시행중의 $^{99m}Tc$-HMPAO 뇌 SPECT는 중대뇌동맥영역의 섭취가 시행전에 비교하여 85%이하인 경우 영구적인 신경학적 결손을 예측할 수 있는 간단하고 객관적인 방법이 될 수 있을 것으로 생각한다.

• 동의생리병리학회지
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• 제17권5호
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• pp.1194-1201
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• 2003

Jaeumgenby-tang(JGT) have been used in oriental medicine for many centries as a therapeutic agent of vertigo caused by deficiency of qi(氣) and blood(血). Effect of Aurantii Fructus(AF) take off the phlegm by promoting the circulation of qi, Gastrodae Rhizoma(GR) has effects treating for headarch, vertigo by calming the liver and suppressing hyperactivity of the liver-yang (陽). I investigated whether injection of JGT adding AFㆍGR extract(JTG) affects cerebral hemodynamics [regional cerebral blood f1ow(rCBF), pial arterial diameter(PAD) in cerebral ischemia rats by MCA occlusion method, and I designed to make manifest whether JTG is mediated by adrenergic β-receptor, cyclooxygenase or guanylate cyclase. The changes of rCBF was determinated by laser-doppler flowmetry(LDF), and the changes of PAD was determinated by video microscope and width analyzer. The results were as follows in cerebral ischemic rats; The changes of rCBF and PAD were increased stabilizly by treatment with JTG(10 ㎎/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with propranolol and indomethacin were increased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. Pretreatment methylene blue was decreased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. In conclusion, JTG causes a diverse response of rCBF and PAD, and action of JTG is mediated by adrenergic β-receptor and cyclooxygenase. I suggest that JTG has an anti-ischemic effect through the improvement of crebral hemodynamics.